Effects of three-dimensional femur and tibia postures on the parameters of standing long-leg radiographs for osteoarthritic knees in elderly female subjects.

BACKGROUND: Long-leg frontal radiographs of the lower extremities are used to assess knee osteoarthritis. Given the three-dimensional (3D) nature of alignment changes in osteoarthritis, postural alterations in the femur and tibia extend beyond the coronal plane (in-plane) to include the transverse and sagittal planes (out-of-plane). This study investigates the impact of these out-of-plane factors on in-plane knee alignment parameters observed in frontal radiographs. METHODS: A total of 97 osteoarthritic knees in women were examined. Using a 3D-to-two-dimensional (2D) image matching technique, we evaluated the 3D postures of the femur and tibia in the standing position as viewed from frontal radiographs in the world coordinate system. Statistical analyses were conducted to explore associations between these 3D postures and 2D alignment parameters obtained from frontal radiographs under identical conditions. FINDINGS: The femur exhibited a medial inclination of 2.7°, a posterior inclination of 3.9°, and an internal rotation of 4.2°, whereas the tibia showed a lateral inclination of 6.4°, an anterior inclination of 6.7°, and an internal rotation of 6.7°. Both coronal and rotational postures of femur and tibia influenced the hip-knee-ankle angle, mechanical axis percentage, and medial proximal tibial angle. However, only coronal factors of tibia impacted tibial joint line obliquity relative to the floor. INTERPRETATION: Attention should be paid to the potential impact of the out-of-plane postures of the femur and tibia on parameters assessed in plain frontal radiographs of the lower extremities.

Usefulness of DXA-based bone strain index in postmenopausal women with type 2 diabetes mellitus.

Bone Strain Index (BSI) is a new dual-energy x-ray absorptiometry (DXA)-based index. We retrospectively evaluated data from 153 postmenopausal women with a history of type 2 diabetes mellitus (T2DM). Lumbar spine and femoral Bone Strain Index (BSI) were sensitive to skeletal impairment in postmenopausal women suffering from T2DM. PURPOSE: Bone Strain Index (BSI) is a new dual-energy X-ray absorptiometry (DXA)-based measurement. We evaluated the performance of BSI in predicting the presence of fragility fractures in type 2 diabetes mellitus (T2DM) postmenopausal women. METHODS: We retrospectively evaluated data from a case-control study of 153 postmenopausal women with a history of at least 5 years of T2DM (age from 40 to 90 years). For each subject, we assessed the personal or familiar history of previous fragility fractures and menopause age, and we collected data about bone mineral density (BMD), BSI, and Trabecular Bone Score (TBS) measurements. Statistical analysis was performed having as outcome the history of fragility fractures. RESULTS: Out of a total of 153 subjects, n = 22 (14.4%) presented at least one major fragility fracture. A negative correlation was found between lumbar BSI and lumbar BMD (r = - 0.49, p < 0.001) and between total femur BSI and total femur BMD (r = - 0.49, p < 0.001). A negative correlation was found between femoral neck BSI and femoral neck BMD (r = - 0.22, p < 0.001). Most DXA-based variables were individually able to discriminate between fractured and non-fractured subjects (p < 0.05), and lumbar BSI was the index with the most relative difference between the two populations, followed by femoral BSI. CONCLUSION: Lumbar spine and femoral BSI are sensitive to skeletal impairment in postmenopausal women suffering from T2DM. The use of BSI in conjunction with BMD and TBS can improve fracture risk assessment.

Does spinopelvic alignment affect femoral head cartilage and the proximal femoral physis in slipped capital femoral epiphysis? A finite element analysis.

BACKGROUND: Slipped capital femoral epiphysis is a prevalent pediatric hip disorder. Recent studies suggest the spine's sagittal profile may influence the proximal femoral growth plate's slippage, an aspect not extensively explored. This study utilizes finite element analysis to investigate how various spinopelvic alignments affect shear stress and growth plate slip. METHODS: A finite element model was developed from CT scans of a healthy adult male lumbar spine, pelvis, and femurs. The model was subjected to various sagittal alignments through reorientation. Simulations of two-leg stance, one-leg stance, walking heel strike, ascending stairs heel strike, and descending stairs heel strike were conducted. Parameters measured included hip joint contact area, stress, and maximum growth plate Tresca (shear) stress. FINDINGS: Posterior pelvic tilt cases indicated larger shear stresses compared to the anterior pelvic tilt variants except in two leg stance. Two leg stance resulted in decreases in the posterior tilted pelvi variants hip contact and growth plate Tresca stress compared to anterior tilted pelvi, however a combination of posterior pelvic tilt and high pelvic incidence indicated larger shear stresses on the growth plate. One leg stance and heal strike resulted in higher shear stress on the growth plate in posterior pelvic tilt variants compared to anterior pelvic tilt, with a combination of posterior pelvic tilt and high pelvic incidence resulting in the largest shear. INTERPRETATION: Our findings suggest that posterior pelvic tilt and high pelvic incidence may lead to increased shear stress at the growth plate. Activities performed in patients with these alignments may predispose to biomechanical loading that shears the growth plate, potentially leading to slip.

Risk of internal fixation treatment in intertrochanteric fracture based on different lateral femoral wall thickness: finite element analysis.

OBJECTIVE: The thickness of the lateral femoral wall, which is an important indicator for evaluating the stability and integrity of intertrochanteric fractures, has been widely studied in recent years. However, as a typical representative of internal fixation treatment, there are few reports on the biomechanical comparison between PFNA and DHS + CS. This study focused primarily on the biomechanical effects of different lateral femoral wall thicknesses on two types of internal fixation through finite element analysis. METHODS: We randomly recruited a healthy adult and collected his femoral CT data to establish a model of femoral intertrochanteric fracture with different lateral femoral wall thicknesses. Following PFNA and DHS + CS fixation, femoral models were simulated, and variations in stress and displacement of the internal fixation and femoral head were recorded under the same physiological load. RESULTS: First, finite element mechanical analysis revealed that the stress and displacement of the internal fixation and femoral head were lower in the femoral model after PFNA fixation than in the DHS + CS model. Second, as the outer wall thickness decreased, the stress and deformation endured by both types of internal fixation gradually increased. CONCLUSIONS: Finite element analysis determined that PFNA exhibits significantly better biomechanical stability than DHS + CS when subjected to varying lateral femoral wall thicknesses. Moreover, lateral femoral wall thickness substantially affects the stability of the two internal fixation biomechanical environments. When the thickness of the lateral femoral wall is too small, we do not recommend using extramedullary fixation because there is a significant risk of internal fixation fracture.

Non-linear association of atherogenic index of plasma with bone mineral density a cross-sectional study.

INTRODUCTION: Although there has been abundant evidence of the association between dyslipidemia as a single factor and osteoporosis, the non-linear relationship between osteoporosis and the Atherogenic Index of Plasma (AIP) has not yet been thoroughly investigated. This study aimed to investigate the complex relationship between AIP and bone mineral density (BMD) to elucidate their interrelationship. METHODS: An analysis of 2007-2018 National Health and Nutrition Survey (NHANES) data was conducted for this study. The study enrolled 5,019 participants. Logarithmically multiplying triglycerides and high-density lipoprotein cholesterol yields the AIP (base 10). The measured variables consisted of BMD in the total femur (TF), femoral neck (FN), and lumbar spine (LS). The association between AIP and BMD was examined using a range of statistical models, such as weighted multivariable logistic regression, generalized additive model, etc. RESULTS: It was found that AIP was positively associated with BMD after adjusting for age, gender, race, socioeconomic status, degree of education, income, Consuming alcoholic beverages, osteoporosis status (Yes or No), ALT, AST, serum creatinine, and total calcium levels. Further studies supported the association link between elevated BMD and AIP. Furthermore, compared to men, females had a higher positive connection between AIP and BMD. In general, there was a curve in the reverse L-shape seen, with a point of change around 0.877, indicating a relationship between AIP and TF BMD. Moreover, a curve exhibiting an L-formed pattern, with a point of inflection at around 0.702, was seen between AIP and FN BMD. In addition, a J-shaped curve was seen, with a point of inflection at 0.092, which demonstrates the association between AIP and LS BMD. CONCLUSION: The AIP and TF BMD curves resemble inverted L shapes, as do the AIP and FN BMD curves. The relationship between AIP and LS BMD was further demonstrated by a J-shaped curve. The results indicate a possible association between AIP and bone mineral density, which should be explored in more detail.

Biomechanical testing of a computationally optimized far cortical locking plate versus traditional implants for distal femur fracture repair.

BACKGROUND: This study experimentally validated a computationally optimized screw number and screw distribution far cortical locking distal femur fracture plate and compared the results to traditional implants. METHODS: 24 artificial femurs were osteotomized with a 10 mm fracture gap 60 mm proximal to the intercondylar notch. Three fixation constructs were used. (i) Standard locking plates secured with three far cortical locking screws inserted according to a previously optimized distribution in the femur shaft (n = 8). (ii) Standard locking plates secured with four standard locking screws inserted in alternating plate holes in the femur shaft (n = 8). (iii) Retrograde intramedullary nail secured proximally with one anterior-posterior screw and distally with two oblique screws (n = 8). Axial hip forces (700 and 2800 N) were applied while measuring axial interfragmentary motion, shear interfragmentary motion, and overall stiffness. FINDINGS: Experimental far cortical locking plate results compared well to published computational findings. Far cortical locking femurs contained the highest axial motion within the potential ideal range of 0.2-1 mm and a sheer-to-axial motion ratio < 1.6 at toe-touch weight-bearing (700 N). At full weight-bearing (2800 N), Standard locking-plated femurs had the only axial motion within 0.2-1 mm but had an excess shear-to-axial motion ratio. Nail-implanted femurs underperformed at both forces. INTERPRETATION: For toe-touch weight-bearing, the far cortical locking construct provided optimal biomechanics to allow moderate motion, which has been suggested to encourage early callus formation. Conversely, at full weight-bearing, the standard locking construct offered the biomechanical advantage on fracture motion.

Site-specific elastic and viscoelastic biomechanical properties of healthy and osteoarthritic human knee joint articular cartilage.

Articular cartilage exhibits site-specific biomechanical properties. However, no study has comprehensively characterized site-specific cartilage properties from the same knee joints at different stages of osteoarthritis (OA). Cylindrical osteochondral explants (n = 381) were harvested from donor-matched lateral and medial tibia, lateral and medial femur, patella, and trochlea of cadaveric knees (N = 17). Indentation test was used to measure the elastic and viscoelastic mechanical properties of the samples, and Osteoarthritis Research Society International (OARSI) grading system was used to categorize the samples into normal (OARSI 0-1), early OA (OARSI 2-3), and advanced OA (OARSI 4-5) groups. OA-related changes in cartilage mechanical properties were site-specific. In the lateral and medial tibia and trochlea sites, equilibrium, instantaneous and dynamic moduli were higher (p < 0.001) in normal tissue than in early and advanced OA tissue. In lateral and medial femur, equilibrium, instantaneous and dynamic moduli were smaller in advanced OA, but not in early OA, than in normal tissue. The phase difference (0.1-0.25 Hz) between stress and strain was significantly smaller (p < 0.05) in advanced OA than in normal tissue across all sites except medial tibia. Our results indicated that in contrast to femoral and patellar cartilage, equilibrium, instantaneous and dynamic moduli of the tibia and trochlear cartilage decreased in early OA. These may suggest that the tibia and trochlear cartilage degrades faster than the femoral and patellar cartilage. The information is relevant for developing site-specific computational models and engineered cartilage constructs.

Automatic segmentation of femoral tumors by nnU-net.

BACKGROUND: Metastatic femoral tumors may lead to pathological fractures during daily activities. A CT-based finite element analysis of a patient's femurs was shown to assist orthopedic surgeons in making informed decisions about the risk of fracture and the need for a prophylactic fixation. Improving the accuracy of such analyses ruqires an automatic and accurate segmentation of the tumors and their automatic inclusion in the finite element model. We present herein a deep learning algorithm (nnU-Net) to automatically segment lytic tumors within the femur. METHOD: A dataset consisting of fifty CT scans of patients with manually annotated femoral tumors was created. Forty of them, chosen randomly, were used for training the nnU-Net, while the remaining ten CT scans were used for testing. The deep learning model's performance was compared to two experienced radiologists. FINDINGS: The proposed algorithm outperformed the current state-of-the-art solutions, achieving dice similarity scores of 0.67 and 0.68 on the test data when compared to two experienced radiologists, while the dice similarity score for inter-individual variability between the radiologists was 0.73. INTERPRETATION: The automatic algorithm may segment lytic femoral tumors in CT scans as accurately as experienced radiologists with similar dice similarity scores. The influence of the realistic tumors inclusion in an autonomous finite element algorithm is presented in (Rachmil et al., "The Influence of Femoral Lytic Tumors Segmentation on Autonomous Finite Element Analyses", Clinical Biomechanics, 112, paper 106192, (2024)).

Effect of experimental pulmonary arterial hypertension on renal and bone parameters of rats submitted to resistance exercise training.

Pulmonary arterial hypertension (PAH) is characterized by right ventricular failure and diminished cardiac output, potentially leading to renal and bone impairments. In contrast, resistance exercise training (RT) offers cardiovascular and bone health benefits. This study aimed to assess the impacts of stable PAH induced by monocrotaline (MCT) and RT on renal morphometry, as well as bone morphometry and biomechanical properties in male Wistar rats. Four experimental groups, untrained control (UC, n=7), trained control (TC, n=7), untrained hypertensive (UH, n=7), trained hypertensive (TH, n=7), were defined. After the first MCT or saline injection (20 mg/kg), trained rats were submitted to a RT program (i.e., Ladder climbing), 5 times/week. Seven days later the rats received the second MCT or saline dose. After euthanasia, renal and femoral histomorphometry and femoral biomechanical properties were assessed. PAH reduced renal glomerular area and volume, which was prevented by the RT. While PAH did not harm the femoral morphometry, structural and mechanical properties, RT improved the femoral parameters (e.g., length, percentage of trabeculae and bone marrow, ultimte and yield loads). Experimental stable PAH promotes renal but not bone damages, whereas RT prevents renal deteriorations and improves the femoral morphological and biomechanical properties.

A preliminary study exploring the mechanical properties of normal and Mgp-deficient mouse femurs during early growth.

Matrix Gla protein (MGP) is mostly known to be a calcification inhibitor, as its absence leads to ectopic calcification of different tissues such as cartilage or arteries. MGP deficiency also leads to low bone mass and delayed bone growth. In the present contribution, we investigate the effect of MGP deficiency on the structural and material mechanical bone properties by focusing on the elastic response of femurs undergoing three-points bending. To this aim, biomechanical tests are performed on femurs issued from Mgp-deficient mice at 14, 21, 28, and 35 days of postnatal life and compared to healthy control femurs. µCT acquisitions enable to reconstruct bone geometries and are used to construct subject-specific finite element models avoiding some of the reported limitations concerning the use of beam-like assumptions for small bone samples. Our results indicate that MGP deficiency may be associated to differences in both structural and material properties of femurs during early stages of development. MGP deficiency appears to be related to a decrease in bone dimensions, compensated by higher material properties resulting in similar structural bone properties at P35. The search for a unique density-elasticity relationship based on calibrated bone mineral density (BMD) indicates that MGP deficiency may affect bone tissue in several ways, that may not be represented uniquely from the quantification of BMD. Despite of its limitation to elastic response, the present preliminary study reports for the very first time the mechanical skeletal properties of Mgp-deficient mice at early stages of development.

Improving the Hip Fracture Risk Prediction with a Statistical Shape-and-Intensity Model of the Proximal Femur.

Severe predictions have been made regarding osteoporotic fracture incidence for the next years, with major economic and social impacts in a worldwide greying society. However, the performance of the currently adopted gold standard for fracture risk prediction, the areal Bone Mineral Density (aBMD), remains moderate. To overcome current limitations, the construction of statistical models of the proximal femur, based on three-dimensional shape and intensity (a hallmark of bone density), is here proposed for predicting hip fracture in a Caucasian postmenopausal cohort. Partial Least Square (PLS)-based statistical models of the shape, intensity and their combination were developed, and the corresponding modes and components were identified. Logistic regression models using the first two shape, intensity and shape-intensity PLS components were implemented and tested within a 10-fold cross-validation procedure as predictors of hip fracture. It emerged that (1) intensity components were superior to shape components in stratifying patients according to their fracture status, and that (2) a combination of intensity and shape improved patients risk stratification. The area under the ROC curve was 0.64, 0.85 and 0.92 for the models based on shape, intensity and shape-intensity combination respectively, against a 0.72 value for the aBMD standard approach. Based on these findings, the presented methodology turns out to be promising in tackling the need for an enhanced fracture risk assessment.

Impact of Internal Malrotation of the Femur Followed by Derotational Osteotomy as Demonstrated by 3D Gait Analysis: A Case Report.

CASE: An 18-year-old man with 48° of internal malrotation of the femur after nailing underwent derotational osteotomy with gait dynamics and electromyography data collected preoperatively and postoperatively. Hip abduction and internal foot progression angles were significantly deviated from normal preoperatively compared with the contralateral side. At 10 months postoperatively, the hip was abducted and externally rotated throughout the entire gait cycle. His Trendelenburg gait had resolved, and he reported no residual functional concerns. Before corrective osteotomy, walking velocity was significantly slower with shorter stride lengths. CONCLUSION: Significant internal malrotation of the femur impairs hip abduction and foot progression angles as well as gluteus medius activation during ambulation. Derotational osteotomy considerably corrected these values.

Individualized cyclic mechanical loading improves callus properties during the remodelling phase of fracture healing in mice as assessed from time-lapsed in vivo imaging.

Fracture healing is regulated by mechanical loading. Understanding the underlying mechanisms during the different healing phases is required for targeted mechanical intervention therapies. Here, the influence of individualized cyclic mechanical loading on the remodelling phase of fracture healing was assessed in a non-critical-sized mouse femur defect model. After bridging of the defect, a loading group (n = 10) received individualized cyclic mechanical loading (8-16 N, 10 Hz, 5 min, 3 × /week) based on computed strain distribution in the mineralized callus using animal-specific real-time micro-finite element analysis with 2D/3D visualizations and strain histograms. Controls (n = 10) received 0 N treatment at the same post-operative time-points. By registration of consecutive scans, structural and dynamic callus morphometric parameters were followed in three callus sub-volumes and the adjacent cortex showing that the remodelling phase of fracture healing is highly responsive to cyclic mechanical loading with changes in dynamic parameters leading to significantly larger formation of mineralized callus and higher degree of mineralization. Loading-mediated maintenance of callus remodelling was associated with distinct effects on Wnt-signalling-associated molecular targets Sclerostin and RANKL in callus sub-regions and the adjacent cortex (n = 1/group). Given these distinct local protein expression patterns induced by cyclic mechanical loading during callus remodelling, the femur defect loading model with individualized load application seems suitable to further understand the local spatio-temporal mechano-molecular regulation of the different fracture healing phases.

A novel technique to assess rotational deformities in lower extremities using CT-based motion analysis.

Rotational deformities following intramedullary (IM) nailing of tibia has a reported incidence of as high as 20%. Common techniques to measure deformities following IM nailing of tibia are either based on clinical assessment, plain X-rays or Computed Tomography (CT) comparing the treated leg with the uninjured contralateral side. All these techniques are based on examiners manual calculation inherently subject to bias. Following our previous rigorous motion analysis and symmetry studies on hemi pelvises, femurs and orthopaedic implants, we aimed to introduce a novel fully digital technique to measure rotational deformities in the lower legs. Following formal institutional approval from the Imperial College, CT images of 10 pairs of human lower legs were retrieved. Images were anonymized and uploaded to a research server. Three dimensional CT images of the lower legs were bilaterally reconstructed. CT-based motion analysis (CTMA) was used and the mirrored images of the left side were merged with the right side proximally as stationary and distally as moving objects. Discrepancies in translation and rotation were automatically calculated. Our study population had a mean age of 54 ± 20 years. There were six males and four females. We observed a greater variation in translation (mm) of Centre of Mass (COM) in sagittal plane (95% CI - 2.959-.292) which was also presented as rotational difference alongside the antero-posterior direction or Y axis (95% CI .370-1.035). In other word the right lower legs in our study were more likely to be in varus compared to the left side. However, there were no statistically significant differences in coronal or axial planes. Using our proposed fully digital technique we found that lower legs of the human adults were symmetrical in axial and coronal plane. We found sagittal plane differences which need further addressing in future using bigger sample size. Our novel recommended technique is fully digital and commercially available. This new technique can be useful in clinical practice addressing rotational deformities following orthopaedic surgical intervention. This new technique can substitute the previously introduced techniques.

Metabolic Profile and Bone Status in Post-Menopausal Women with Rheumatoid Arthritis: A Monocentric Retrospective Survey.

Background: Rheumatoid arthritis (RA) and metabolic syndrome (MetS) are chronic conditions that share common inflammatory mechanisms. Both diseases can lead to an impairment of the bone microarchitecture. The aims of our study were to evaluate clinical, metabolic, and bone parameters in RA patients with or without MetS (MetS+, MetS-) and potential correlations between the glico-lipidic profile, RA disease activity, and bone status. Methods: A total of thirty-nine RA female post-menopausal patients were recruited (median age 66.6 ± 10.4, disease duration 3 ± 2.7). Anthropometric data, medical history, and current treatment were recorded along with basal blood tests, bone, and lipid metabolism biomarkers. RA disease activity and insulin resistance were evaluated through standard scores. Quantitative assessment of the bone (bone mineral density-BMD) was performed by dual-energy-X ray absorption (DXA), whereas bone quality was quantified with the trabecular bone score (TBS). Results: No statistically significant differences concerning both BMD and TBS were detected between the MetS+ and MetS- RA patients. However, the MetS+ RA patients exhibited significantly higher disease activity and lower serum 25-hydroxyvitamin D [25(OH)D] concentrations (respectively, p = 0.04 and p = 0.01). In all RA patients, a significant negative correlation emerged between the BMD of the femoral trochanter with plasmatic triglycerides (TG) concentrations (r = -0.38, p = 0.01), whereas the lumbar BMD was positively correlated with the abdominal waist (AW) and fasting glucose (FG) concentrations. On the other hand, the TBS was negatively correlated with insulin concentrations, FG, and RA disease activity (respectively, r = -0.45, p = 0.01, r = -0.40, p = 0.03, r = -0.37, p = 0.04), the last one was further negatively correlated with 25-OHD serum concentrations (r = -0.6, p = 0.0006) and insulin-resistance (r = 0.3, p = 0.04). Conclusions: Bone quantity (BMD) and quality (TBS) do not seem significantly changed among MetS+ and MetS- RA patients; however, among MetS+ patients, both significantly higher disease activity and lower vitamin D serum concentrations were observed. In addition, the significant negative correlations between the alterations of metabolic parameters limited to the TBS in all RA patients might suggest that qualitative bone microarchitecture impairments (TBS) might manifest despite unchanged BMD values.

The Influence of Femoral Internal Rotation on Patellar Tracking in Total Knee Arthroplasty Using Gap Technique.

BACKGROUD: Femoral internal rotation in total knee arthroplasty (TKA) is well known as one of the main causes of patellar maltracking. Although femoral internal rotation in TKA is considered unacceptable due to the risk of patellar maltracking, it is sometimes required for ligament balancing. We evaluated the influence of femoral internal rotation on patellar tracking in TKA performed using the gap technique. METHODS: From April 2008 to May 2018, 1,612 cases of TKA were done. Among them, 245 cases of TKA for osteoarthritis were followed up for at least 1 year and included in this study. We compared patellar tracking in two groups; group I consisted of 99 cases whose femoral rotation was less than 0° and group II consisted of 146 cases whose femoral rotation was 3°-5° external rotation. Preoperative femoral rotation was measured with the condylar twist angle (CTA) by using computed tomography. The patella was replaced in all cases. Patellar tracking was evaluated with patellar tilt angle (lateral tilt [+] and medial tilt [-]) in the merchant radiograph. Statistical analysis was done using Mann-Whitney U-test. Clinical assessment was performed using the Knee Society clinical rating system. RESULTS: The preoperative CTA was 5.3° ± 1.6° in group I and 5.4° ± 1.6° in group II, showing no statistically significant difference between groups (p = 0.455). Intraoperative femoral rotation was -0.5° ± 0.8° in group I and 3.9° ± 0.8° in group II when the gap technique was used (p < 0.001). The postoperative patellar tilt angle was -0.4° ± 3.6° in group I and 0.1° ± 4.1° in group II with no statistically significant difference (p = 0.251). CONCLUSIONS: Compared with femoral external rotation, femoral internal rotation with ligament balance in TKA was not more associated with patellar maltracking. Therefore, patellar tracking might be related with ligament balance in flexion regardless of the anatomic femoral rotational alignment.

Elastic, Dynamic Viscoelastic and Model-Derived Fibril-Reinforced Poroelastic Mechanical Properties of Normal and Osteoarthritic Human Femoral Condyle Cartilage.

Osteoarthritis (OA) degrades articular cartilage and weakens its function. Modern fibril-reinforced poroelastic (FRPE) computational models can distinguish the mechanical properties of main cartilage constituents, namely collagen, proteoglycans, and fluid, thus, they can precisely characterize the complex mechanical behavior of the tissue. However, these properties are not known for human femoral condyle cartilage. Therefore, we aimed to characterize them from human subjects undergoing knee replacement and from deceased donors without known OA. Multi-step stress-relaxation measurements coupled with sample-specific finite element analyses were conducted to obtain the FRPE material properties. Samples were graded using OARSI scoring to determine the severity of histopathological cartilage degradation. The results suggest that alterations in the FRPE properties are not evident in the moderate stages of cartilage degradation (OARSI 2-3) as compared with normal tissue (OARSI 0-1). Drastic deterioration of the FRPE properties was observed in severely degraded cartilage (OARSI 4). We also found that the FRPE properties of femoral condyle cartilage related to the collagen network (initial fibril-network modulus) and proteoglycan matrix (non-fibrillar matrix modulus) were greater compared to tibial and patellar cartilage in OA. These findings may inform cartilage tissue-engineering efforts and help to improve the accuracy of cartilage representations in computational knee joint models.

Serum PTH, PTH1R/ATF4 pathway, and the sRANKL/OPG system in bone as a new link between bone growth, cross-sectional geometry, and strength in young rats with experimental chronic kidney disease.

The progression of chronic kidney disease (CKD) in children is associated with deregulated parathyroid hormone (PTH), growth retardation, and low bone accrual. PTH can cause both catabolic and anabolic impact on bone, and the activating transcription factor 4 (ATF4), a downstream target gene of PTH, is related to its anabolic effect. Osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) are PTH-dependent cytokines, which may play an important role in the regulation of bone remodeling. This study aimed to evaluate the impact of endogenous PTH and the bone RANKL/OPG system on bone growth, cross-sectional geometry and strength utilizing young, nephrectomized rats. The parameters of cross-sectional geometry were significantly elevated in rats with CKD during the three-month experimental period compared with the controls, and they were strongly associated with serum PTH levels and the expression of parathyroid hormone 1 receptor (PTH1R)/ATF4 genes in bone. Low bone soluble RANKL (sRANKL) levels and sRANKL/OPG ratios were also positively correlated with cross-sectional bone geometry and femoral length. Moreover, the analyzed geometric parameters were strongly related to the biomechanical properties of femoral diaphysis. In summary, the mild increase in endogenous PTH, its anabolic PTH1R/ATF4 axis and PTH-dependent alterations in the bone RANKL/OPG system may be one of the possible mechanisms responsible for the favorable impact on bone growth, cross-sectional geometry and strength in young rats with experimental CKD.

Rhizomelia and Impaired Linear Growth in a Girl with Juvenile Paget Disease: The Natural History of the Condition.

In ultra-rare bone diseases, information on growth during childhood is sparse. Juvenile Paget disease (JPD) is an ultra-rare disease, characterized by loss of function of osteoprotegerin (OPG). OPG inhibits osteoclast activation via the receptor activator of nuclear factor-κB (RANK) pathway. In JPD, overactive osteoclasts result in inflammatory-like bone disease due to grossly elevated bone resorption. Knowledge on the natural history of JPD, including final height and growth, is limited. Most affected children receive long-term antiresorptive treatment, mostly with bisphosphonates, to contain bone resorption, which may affect growth. In this study, we report the follow-up of height, growth velocity, and skeletal maturation in a 16-year-old female patient with JPD. The patient was treated with cyclic doses of pamidronate starting at 2.5 years of age and with 2 doses of denosumab at the age of 8 years, when pamidronate was paused. In the following years, a sustainable decline in a height z-score and a stunted pubertal growth spurt; despite appropriate maturation of the epiphyseal plates of the left hand, the proximal right humerus and both femora were observed. Whether this reflects the growth pattern in JPD or might be associated to the antiresorptive treatments is unclear, since there is very limited information available on the effect of bisphosphonates and denosumab on growth and the growth plate in pediatric patients. Studies are needed to understand the natural history of an ultra-rare bone disease and to assess the effects of antiresorptive treatment on the growing skeleton.

Radiocapitellar joint pressures following transradial amputation increase during elbow motion.

This study aimed to compare the contact area, mean pressure, and peak pressure of the radiocapitellar joint (RCJ) in the upper limb after transradial amputation with those of the normal upper limb during elbow flexion and forearm rotation. Testing was performed using ten fresh-frozen upper limbs, and the transradial amputation was performed 5 cm proximal to the radial styloid process. The specimens were connected to a custom-designed apparatus for testing. A pressure sensor was inserted into the RCJ. The biomechanical indices of the RCJ were measured during elbow flexion and forearm rotation in all specimens. There was no significant difference in the contact area between the normal and transradial amputated upper limbs. However, in the upper limbs after transradial amputation, the mean pressure was higher than that in the normal upper limbs at all positions of elbow flexion and forearm rotation. The peak pressure was significantly higher in the upper limbs after transradial amputation than in the normal upper limbs, and was especially increased during pronation at 45° of elbow flexion. In conclusion, these results could cause cartilage erosion in the RCJ of transradial amputees. Thus, methods to reduce the pressure of the RCJ should be considered when a myoelectric prosthesis is developed.