People with severe degenerative conditions, such as osteoarthritis (OA), have been shown to have altered movement patterns during sit-to-stand. However it remains unclear whether such alterations exist in people with early OA, in the absence of pain. This study aimed to determine if a novel seat could be used to discriminate people with early OA compared with controls. The sit-to-stand task was performed by 20 people with early medial knee OA and 20 age and gender-matched control subjects, using an instrumented seat. OA subjects showed altered weight distribution in the transition phase from sit to stand, in that they placed more load through their unaffected side. Task duration was also significantly longer for OA subjects. This study has demonstrated that a novel instrumented seat can be used to discriminate people with early medial knee OA during the sit-to-stand activity. These results may be relevant for early interventions to delay or prevent changes in muscle function of the affected limb as well as contralateral knee or hip osteoarthritis in these patients.

Abstract. Objective. Explore whether high tibial osteotomy (HTO) changes knee contact forces and to explore the relationship between the external knee adduction moment (EKAM) pre and 12 months post HTO. Methods. Three-dimensional gait analysis was performed on 17 patients pre and 12-months post HTO using a modified Cleveland marker-set. Tibiofemoral contact forces were calculated in SIMM. The scaled musculoskeletal model integrated an extended knee model allowing for 6 degrees of freedom in the tibiofemoral and patellofemoral joint. Joint angles were calculated using inverse kinematics then muscle and contact forces and secondary knee kinematics were estimated using the COMAC algorithm. Paired samples t-test were performed using SPSS version 25 (SPSS Inc., USA). Testing for normality was undertaken with Shapiro-Wilk. Pearson correlations established the relationships between EKAM1 to medial KCF1, and EKAM2 to medial KCF2, pre and post HTO. Results. Total knee contact force peak 1 significantly reduced from 2.6 x body weight pre-HTO to 2.3 x body weight 12-months post-HTO. Medial contact force peak 1 significantly reduced from 1.7 x body weight pre-HTO to 1.5 x body weight 12-months post-HTO. Second peak lateral knee contact force significantly increased from 0.9 body weight pre-HTO to 1.1 x body weight 12-months post-HTO. Furthermore, this study found very strong correlations between EKAM1 and medial KCF1 pre-HTO (r=0.85) as well as post-HTO (r=0.91). There was a significantly moderate relationship between EKAM2 and medial KCF2 pre-HTO (r=0.625). Conclusion. HTO significantly reduced overall and medial KCF during the first half of stance whilst increasing second half of stance peak lateral knee contact force. This study demonstrated a strong relationship between EKAM peaks and respective medial KCF peaks, supporting the usefulness of EKAM as a surrogate measure of medial compartment tibiofemoral contact forces. This demonstrates HTO successfully offloads the tibiofemoral joint overall, as well as offloading the medial compartment

Hop tests are used to determine return to sports after ACL reconstruction. They mostly measure distance and symmetry but do not assess kinematics and kinetics. Recently, biomechanical evaluations have been incorporated into these functional jump tests for the better assessment of return to sport. We assessed the sagittal plane range of motion (ROM) of the knee, the deviation axis of rotation (DAOR), and the vertical ground reaction force (vGRF) normalized to body weight in nine healthy participants during the single leg (SLH) and crossover hop tests (COHT). Participants' leg lengths were measured. Jumping distances were marked in the test area as being 4/5 of the leg length. Four sensors were placed on the thighs, the legs and the feet. These body parts were handled as a single rigid body. Eight 480 Hz cameras were used to capture the movements of these rigid bodies. vGRF at landing were measured using a force plate (Bertec, Inc, USA). The ROM of the knee joint and the DAOR were obtained from kinematic data. Participants' joint kinematics metrics were similar in within-subjects statistical tests for SLH and COHT. We therefore asked whether the repeated vGRF normalized to body weight will be similar in both legs during these jumps. Joint kinematics metrics however were different in between subjects indicating the existence of a personalized jumping strategy. These hop tests can be recorded at the beginning of the training season for each individual, which can establish a comparative evaluation database for prospective lower extremity injury recovery and return to sport after ACL injury

Osteoarthritis (OA) affects the whole joint and leads to chronic pain. The sympathetic nervous system (SNS) seems to be involved in OA pathogenesis, as indicated by in vitro studies as well as by our latest work demonstrating that sympathectomy in mice results in increased subchondral bone volume in the OA knee joint. We assume that chronic stress may lead to opposite effects, such as an increased bone loss in OA due to an elevated sympathetic tone. Therefore, we analyzed experimental OA progression in mice exposed to chronic stress. OA was induced in male C57BL/6J mice by surgical destabilization of the medial meniscus (DMM) and Sham as well as non-operated mice served as controls. Half of these groups were exposed to chronic unpredictable mild stress (CUMS). After 12 weeks, chronic stress efficiency was assessed using behavioral tests. In addition to measuring body weight and length, changes in subchondral bone were analyzed by μCT. Dynamic Weight Bearing system was used to monitor OA-related pain. Histological scoring will be conducted to investigate the severity cartilage degeneration and synovial inflammation. CUMS resulted in increased anxiety and significant decrease in body weight gain in all CUMS groups compared to non-CUMS groups. CUMS also increased serum corticosterone in healthy mice, with even higher levels in CUMS mice after DMM surgery. CUMS had no significant effect on subchondral bone, but subarticular bone mineral density and trabecular thickness were increased. Moreover, CUMS resulted in significant potentiation of DMM-associated pain. Our results suggest that the autonomic imbalance with increased sympathetic nervous activity induced by chronic stress exacerbates the severity of OA pain perception. We expect significantly increased cartilage degeneration as well as more severe synovial inflammation in CUMS DMM mice compared to DMM mice

The objective of this study was to use patient-specific finite element modeling to measure the 3D interfragmentary strain environment in clinically realistic fractures. The hypothesis was that in the early post-operative period, the tissues in and around the fracture gap can tolerate a state of strain in excess of 10%, the classical limit proposed in the Perren strain theory. Eight patients (6 males, 2 females; ages 22–95 years) with distal femur fractures (OTA/AO 33-A/B/C) treated in a Level I trauma center were retrospectively identified. All were treated with lateral bridge plating. Preoperative computed tomography scans and post-operative X-rays were used to create the reduced fracture models. Patient-specific materials properties and loading conditions (20%, 60%, and 100% body weight (BW)) were applied following our published method.[1]. Elements with von Mises strains >10% are shown in the 100% BW loading condition. For all three loading scenarios, as the bridge span increased, so did the maximum von Mises strain within the strain visualization region. The average gap closing (Perren) strain (mean ± SD) for all patient-specific models at each body weight (20%, 60%, and 100%) was 8.6% ± 3.9%, 25.8% ± 33.9%, and 39.3% ± 33.9%, while the corresponding max von Mises strains were 42.0% ± 29%, 110.7% ± 32.7%, and 168.4% ± 31.9%. Strains in and around the fracture gap stayed in the 2–10% range only for the lowest load application level (20% BW). Moderate loading of 60% BW and above caused gap strains that far exceeded the upper limit of the classical strain rule (<10% strain for bone healing). Since all of the included patients achieved successful unions, these findings suggest that healing of distal femur fractures may be robust to localized strains greater than 10%

Introduction. Osteoarthritis (OA) is a chronic degenerative disease of the entire joint leading to joint stiffness and pain (PMID:33571663). Recent evidence suggests that the sympathetic nervous system (SNS) plays a role in the pathogenesis of OA (PMID:34864169). A typical cause for long-term hyperactivity of the SNS is chronic stress. To study the contribution of increased sympathetic activity, we analyzed the progression of OA in chronically stressed mice. Method. We induced OA in male C57BL/6J mice by destabilizing the medial meniscus (DMM)(PMID:17470400) and exposed half of these mice to chronic unpredictable mild stress (CUMS)(PMID:28808696). Control groups consisted of sham-operated mice with and without CUMS exposure. After 12 weeks, CUMS efficacy was determined by assessing changes in body weight gain and activity of mice, measuring splenic norepinephrine and serum corticosterone levels. OA progression was studied by histological analysis of cartilage degeneration and synovitis, and by μCT to evaluate changes in calcified cartilage and subchondral bone microarchitecture. A dynamic weight-bearing system was used to assess OA-related pain. Result. CUMS resulted in significantly decreased body weight gain and activity, as well as increased splenic norepinephrine and serum corticosterone concentrations compared to the respective controls. Surprisingly, already DMM alone resulted in elevated stress hormone levels. CUMS significantly exacerbated cartilage degeneration and synovial inflammation and increased OA pain in DMM mice. The underlying cellular and molecular mechanisms are currently being analyzed using FACS, single cell RNAseq, and spatial proteomics. Conclusion. Overall, chronic stress exacerbates OA severity and pain. Moreover, increased levels of stress hormones were observed in OA mice without CUMS induction, suggesting a complex bi-directional interaction between the SNS and OA. Targeting the autonomic nervous system, such as attenuating the SNS but also stimulating the activity of the parasympathetic nervous system, as a counterpart of the SNS, may therefore be promising for novel preventive or causal treatments of OA

Introduction. Understanding knee joint biomechanics is crucial, but studying Anterior cruciate ligament (ACL) biomechanics in human adolescents is challenging due to limited availability cadaveric specimens. This study aims to validate the adolescent porcine stifle joint as a model for ACL studies by examining the ACL's behavior under axial and torsion loads and assessing its deformation rate, stiffness, and load-to-failure. Methods. Human knee load during high-intensity sports can reach 5-6 times body weight. Based on these benchmarks, the study applied a force equivalent to 5-times body weight of juvenile porcine samples (90 pounds), estimating a force of 520N. Experiments involved 30 fresh porcine stifle joints (Yorkshire breed, Avg 90 lbs, 2-4 months old) stored at -22°C, then thawed and prepared. Joints were divided into three groups: control (load-to-failure test), axially loaded, and 30-degree torsion loaded. Using a servo-hydraulic material testing machine, the tibia's longitudinal axis was aligned with the load sensor, and specimens underwent unidirectional tensile loading at 1 mm/sec until rupture. Data on load and displacement were captured at 100 Hz. Results. One-way ANOVA showed statistically significant differences in maximum failure force among loading conditions (p = 0.0039). Post hoc analysis indicated significant differences between the control and 500N (non-twisted) groups (p = 0.014) and between the control and 500N (twisted) groups (p = 0.003). However, no significant difference was found between 500N (non-twisted) and 500N (twisted) groups (p = 0.2645). Two samples broke from the distal femur growth plates, indicating potential growth plate vulnerability in adolescent porcines. Conclusions. The study validates the adolescent porcine stifle joint as a suitable model for ACL biomechanical research, demonstrating that torsional loads are as damaging to the ACL's integrity as equivalent axial loads. It also highlights the potential vulnerability of growth plates in younger populations, reflected in the porcine model

Introduction. Many patients with obesity experience knee pain. Excess body weight is a modifiable risk factor for osteoarthritis (OA) and weight loss is encouraged in patients with OA. Bariatric surgery could improve or limit the progression of these conditions through significant weight loss. The Oxford Knee Score (OKS) is a validated tool in the assessment of knee replacement surgery for OA. We present a novel application of the OKS to assess knee pain & function after weight loss surgery. The primary aim of this study was to assess whether there was a significant difference in mean OKS before and 24 months after weight loss surgery. Method. Eighteen female participants were included in this study. They underwent sleeve gastrectomy or Roux-en-Y gastric bypass. Patient demographics, body mass index (BMI) and OKS were collected pre- and 24 months post operatively. Result. There was an increase in the mean OKS from 31.8 (SD 11.8) pre surgery to 36.6 (SD 12.3) at 24 months. This was statistically significant (95% CI 0.99-10.5, p=0.02). Mean BMI reduced from 46.6 kg/m. 2. (SD 5.8) to 33.0 kg/m. 2. (SD 3.5). Conclusion. A significant improvement in mean OKS was seen after weight loss surgery. These findings demonstrate an improvement in knee pain & function with weight loss. This study contributes to a larger project evaluating the kinetic and kinematic changes to walking gait from weight loss

The effect of high-fat diet and testosterone replacement therapy upon bone remodelling was investigated in orchiectomised male APOE-/- mice. Mice were split in to three groups: sham surgery + placebo treatment (control, n=9), orchiectomy plus placebo treatment (n=8) and orchiectomy plus testosterone treatment (n=10). Treatments were administered via intramuscular injection once a fortnight for 17 weeks before sacrifice at 25 weeks of age. Tibiae were scanned ex-vivo using µCT followed by post-analysis histology and immunohistochemistry. Previously presented µCT data demonstrated orchiectomised, placebo treated mice exhibited significantly reduced trabecular bone volume, number, thickness and BMD compared to control mice despite no significant differences in body weight. Trabecular parameters were rescued back to control levels in orchiectomised mice treated with testosterone. No significant differences were observed in the cortical bone. Assessment of TRAP stained FFPE sections revealed no significant differences in osteoclast or osteoblast number along the endocortical surface. IHC assessment of osteoprotegerin (OPG) expression in osteoblasts is to be quantified alongside markers of osteoclastogenesis including RANK and RANKL. Results support morphological analysis of cortical bone where no change in cortical bone volume or density between groups is in line with no significant change in osteoblast or osteoclast number and percentage across all three groups. Future work will include further IHC assessment of bone remodelling and adiposity, as well as utilisation of mechanical testing to establish the effects of observed morphological differences in bone upon mechanical properties. Additionally, the effects of hormone treatments upon murine-derived bone cells will be investigated to provide mechanistic insights

3D accurate measurements of the skeletal structures of the foot, in physiological and impaired subjects, are now possible using Cone-Beam CT (CBCT) under real-world loading conditions. In detail, this feature allows a more realistic representation of the relative bone-bone interactions of the foot as they occur under patient-specific body weight conditions. In this context, varus/valgus of the hindfoot under altered conditions or the thinning of plantar tissues that occurs with advancing age are among the most complex and interesting to represent, and numerous measurement proposals have been proposed. This study aims to analyze and compare these measurements from CBCT in weight-bearing scans in a clinical population. Sixteen feet of diabetic patients and ten feet with severe adult flatfoot acquired before/after corrective surgery underwent CBCT scans (Carestream, USA) while standing on the leg of interest. Corresponding 3D shapes of each bone of the shank and hindfoot were reconstructed (Materialise, Belgium). Six different techniques found in the literature were used to calculate the varus/valgus deformity, i.e., the inclination of the hindfoot in the frontal plane of the shank, and the distance between the ground and the metatarsal heads was calculated along with different solutions for the identification of possible calcifications. Starting with an accurate 3D reconstruction of the skeletal structures of the foot, a wide range of measurements representing the same angle of hindfoot alignment were found, some of them very different from each other. Interesting correlations were found between metatarsal height and subject age, significant in diabetic feet for the fourth and fifth metatarsal bones. Finally, CBCT allows 3D assessment of foot deformities under loaded conditions. The observed traditional measurement differences and new measurement solutions suggest that clinicians should consider carefully the anatomical and functional concepts underlying measurement techniques when drawing clinical and surgical conclusions

Low back pain (LBP) is a worldwide leading cause of disability. Treatment of intervertebral disc (IVD) with stem cells has been used on degenerate discs (IDD), cause of around 40% of LBP cases. Despite pain reduction, clinical studies' follow-up have not shown a structural IVD improvement. A valid alternative may be the use of notocordal cells (NC) or their precursors. Mesendoderm progenitor cells (MEPC) have the ability to replicate and differentiate toward NC. In this preliminary study we evaluated in a preclinical IDD model the viability and NC differentiation of MEPC derived from induced pluripotent stem cells (iPSC). MEPC derived from iPSC were developed during the iPSpine project (# 825925), thawed, plated for 24h on laminin and labeled with PKH26. Two adult sheep were subjected to nucleotomy of five lumbar discs for the induction of IDD. After 5 weeks, 3 degenerated discs were treated with MEPC at 3 different doses (low, medium and high). One sheep was sacrificed after 7 days and one after 30 days. Clinical parameters were collected to evaluate the safety of treatment. Discs were analysed using histological techniques. Survival (PKH26), proliferation (PCNA), notocordal cell differentiation (Brachyury, Cytokeratin 8/18/19, Sox9, Foxa2) and endodermal differentiation (Sox17) were evaluated. At 7 days from treatment, both sheep lost about 20% of body weight. Only in discs treated with the highest dose PKH26 stained cells were alive up to 30 days. These cells turn out to be: proliferating (PCNA); positive for Brachyury, cytokeratin 8/18/19 and Foxa2; positive for SOX17 in a small percentage. This preliminary study shows that MEPC, derived from iPSC and injected into ovine discs degenerated by nucleotomy, are able to survive up to 30 days and differentiate within the disc predominantly towards the notocordal phenotype

This study examined pre-operative measures to predict post-operative biomechanical outcomes in total knee arthroplasty (TKA) patients. Twenty-eight patients (female=12/male=16, age=63.6±6.9, BMI=29.9±7.4 kg/m2) with knee osteoarthritis scheduled to undergo TKA were included. All surgeries were performed by the same surgeon (GD) with a subvastus approach. Patients visited the gait lab within one-month prior to surgery and 12 months following surgery. At the gait lab, patients completed the knee injury and osteoarthritis outcome score (KOOS), a timed up and go (TUG), maximum knee flexion and extension strength evaluation, and a walking task. Variables of interest included the five KOOS sub-scores, TUG time, maximum knee flexion and extension strength normalized to body weight, walking speed, and peak knee biomechanics variables (flexion angle, abduction moment, power absorption). A Pearson's correlation was used to identify significantly correlated variables which were then inputted into a multiple regression. No assumption violations for the multiple regression existed for any variables. Pre-operative knee flexion and extension strength, TUG time, and age were used in the multiple regression. The multiple regression model statistically significantly predicted peak knee abduction moment, post-operative walking speed, and post-operative knee flexion strength. All four variables added statistically significantly to the prediction p<.05. Pre-operative KOOS values did not correlate with any biomechanical indicators of post-operative success. Age, pre-operative knee flexion and extension strength, and TUG times predicted peak knee abduction moment, which is associated with medial knee joint loading. These findings stress the importance of pre-surgery condition, as stronger individuals achieved better post-operative biomechanical outcomes. Additionally, younger patients had better outcomes, suggesting that surgeons should not delay surgery in younger patients. This delay in surgery may prevent patients from achieving optimal outcomes. Future studies should utilize a hierarchical multiple regression to identify which variables are most predictive

Low back pain (LBP) is the leading cause of disability worldwide. Recently, treatment of the intervertebral disc (IVD) with stem cells has been used for the treatment of degenerate discs (IDD) which cause at least the 40% of LBP cases. Despite pain reduction, follow-up in clinical studies have not shown an improvement in the structural integrity of IVD. A valid alternative could be the use of progenitor disc cells (notocordal cells, NC) or of their precursors. Mesendoderm progenitor cells (MEPC) have the ability to replicate and differentiate toward NC. In this preliminary study we evaluated in a preclinical large animal IDD model the viability and NC differentiation of MEPC derived from induced pluripotent stem cells (iPSC). MEPC, derived from iPSC and developed during the iPSpine project (# 825925), were thawed and plated on laminin for 24h and labeled with PKH26. Two adult sheep were subjected to nucleotomy of five lumbar discs for the induction of IDD. After 5 weeks, 3 of the 5 degenerate discs were treated with MEPC at 3 different doses (low, medium and high). One sheep was sacrificed after 7 days and the other after 30 days from the treatment injection procedure. Clinical parameters were collected to evaluate the safety of treatment. Discs were paraffin embedded and analysed using histological techniques. Survival (PKH26), proliferation (PCNA), notocordal cell differentiation (Brachyury, Cytokeratin 8/18/19, Sox9, Foxa2) and endodermal differentiation (Sox17) were evaluated. After the injection of the cells, both sheep lost about 20% of body weight. The analysis showed that only in discs treated with the highest dose the PKH26 stained cells resulted alive after 30 days from the procedure. These cells turn out to be:. -. in proliferation (PCNA). -. positive for Brachyury, cytokeratin 8/18/19 and Foxa2. -. a small percentage positive for SOX17. This preliminary study shows that MEPC, derived from iPSC and injected into ovine discs degenerated by nucleotomy, are able to survive 30 days from treatment and differentiate within the disc predominantly towards the notocordal phenotype

Introduction and Objective. Low back pain (LBP) is a major cause of long-term disability in adults worldwide and it is frequently attributed to intervertebral disc (IVD) degeneration. So far, no consensus has been reached regarding appropriate treatment and LBP management outcomes remain disappointing. Spine unloading or traction protocols are common non-surgical approaches to treat LBP. These treatments are widely used and result in pain relief, decreased disability or reduced need for surgery. However, the underlying mechanisms -namely, the IVD unloading mechanobiology- have not yet been studied. The aim of this first study was to assess the feasibility of IVD unloading in a large animal organ culture set-up and evaluate its impact on mechanobiology. Materials and Methods. Bovine tail discs (diameter 16.1 mm ± 1.2 mm), including the endplates, were isolated and prepared for culture. Beside the day0 sample that was processed directly, three other discs were cultured for 3 days and processed on day4. One disc was loaded in the bioreactor according to a previously established physiological (compressive) loading protocol (2h/day, 0.2Hz). The two other discs were embedded in biocompatible resin, leaving the cartilage endplate free to permit nutrient diffusion, and fitted in the traction holder; one of these discs was kept in free swelling conditions, whereas the second was submitted to cyclic traction loading (2h/day, 0.2Hz) corresponding to 30% of the animal body weight corrected for organ culture. Results. The cell viability assessed on lactate dehydrogenase and ethidium homodimer stained histological slides was not different between the three cultured discs. This means that the disc viability was not affected neither by the embedding, nor by the traction itself. Compared to the physiologically loaded disc, the gene expression of COL1, COL2 and ACAN was higher in the nucleus pulposus and inner annulus fibrosus of the traction treated disc. In the outer annulus fibrosus of this disc TAGLN and MKX were higher expressed upon traction than in the physiologically loaded disc. Conclusions. Based on these preliminary data, we can conclude that large animal organ culture allows effective unloading of the disc, while preserving cell viability and modulating cellular gene expression responses. This sets the ground for future experiments and opens the door to an evidence-based improvement of clinical spine traction protocols and LBP management overall

Introduction and Objective. Chronic tendinopathy is a multifactorial disease and a common problem in both, athletes and the general population. Mechanical overload and in addition old age, adiposity, and metabolic disorders are among the risk factors for chronic tendinopathy but their role in the pathogenesis is not yet unequivocally clarified. Materials and Methods. Achilles tendons of young (10 weeks) and old (100 weeks) female rats bred for high (HCR) and low (LCR) intrinsic aerobic exercise capacity were investigated. Both Achilles tendons of 28 rats were included and groups were young HCR, young LCR, old HCR, and old LCR (n = 7 tendons per group/method). In this rat model, genetically determined aerobic exercise capacity is associated with a certain phenotype as LCR show higher body weight and metabolic dysfunctions in comparison to HCR. Quantitative real-time PCR (qPCR) was used to evaluate alterations in gene expression. For histological analysis, semi-automated image analysis and histological scoring were performed. Results. Age-related downregulation of tenocyte marker genes (Tenomodulin), genes related to matrix modelling and remodeling (Collagen type 1, Collagen type 3, Elastin, Biglycan, Fibronectin, Tenascin C), and Transforming growth factor beta 3 (Tgfb3) were detected in tendons from HCR and LCR. Furthermore, inflammatory marker Cyclooxygenase 2 (Cox2) was downregulated, while Microsomal prostaglandin E synthase 2 (Ptges2) was upregulated in tendons from old HCR and old LCR. No significant alteration was seen in Interleukin 6 (Il6), Interleukin 1 beta (Il1b), and Tumor necrosis factor alpha (Tnfa). Histological analysis revealed that Achilles tendons of old rats had fewer and more elongated tenocyte nuclei compared to young rats, indicating a reduced metabolic activity. Even though higher content of glycosaminoglycans as a sign of degeneration was found in tendons of old HCR and LCR, no further signs of tendinopathy were detectable in histological evaluation. Conclusions. Overall, aging seems to play a prominent role in molecular and structural alterations of Achilles tendon tissue, while low intrinsic exercise capacity did not cause any changes. Even though tendinopathy was not present in any of the groups, some of the shown age-related changes correspond to single characteristics of chronic tendon disease. This study gives an insight into tendon aging and its contribution to molecular and cellular changes in Achilles tendon tissue

Introduction and Objective. Global prevalence of obesity has risen almost three-fold between 1975 and 2016. Alongside the more well-known health implications of obesity such as cardiovascular disease, cancer and type II diabetes, is the effect of male obesity on testosterone depletion and hypogonadism. Hypogonadism is a well-known contributor to the acceleration of bone loss during aging, and obesity is the single biggest risk factor for testosterone deficiency in men. Understanding the micro and macro structural changes to bone in response to testosterone depletion in combination with a high fat ‘Western’ diet, will advance our understanding of the relationship between obesity and bone metabolism. This study investigated the impact of surgically induced testosterone depletion and subsequent testosterone treatment upon bone remodelling in mice fed a high fat diet. Materials and Methods. Male ApoE. −/−. mice were split into 3 groups at 7 weeks of age and fed a high fat diet: Sham surgery with placebo treatment, orchiectomy surgery with placebo treatment, and orchiectomy surgery with testosterone treatment. Surgeries were performed at 8 weeks of age, followed by fortnightly testosterone treatment via injection. Mice were sacrificed at 25 weeks of age. Tibiae were collected and scanned ex-vivo at 4.3μm on a SkyScan 1272 Micro-CT scanner (Bruker). Left tibiae were used for assessment of trabecular and cortical Volumes of Interest (VOIs) 0.2mm and 1.0mm respectively from the growth-plate bridge break. Tibiae were subsequently paraffin embedded and sectioned at 4μm prior to immunohistochemical evaluation of alkaline phosphatase. Results. Trabecular bone volume and mineral density were significantly reduced in orchiectomised mice compared to sham-operated controls; and these parameters were normalised to control levels in orchiectomised mice treated with testosterone. In contrast, Trabecular thickness was significantly higher in testosterone depleted animals. Cortical bone parameters and body weights did not significantly differ between groups. Levels of alkaline phosphatase did not differ significantly in cortical or trabecular osteoblasts between groups. Conclusions. Findings suggest that testosterone deficiency significantly reduces trabecular bone parameters, and testosterone therapy may be a useful intervention for the loss of bone mass in testosterone deficient males. These results indicate that testosterone therapy may be useful for the treatment of trabecular bone frailty in testosterone deficient males. Observed changes in trabecular bone do not appear to be due to decreased mineralisation caused by osteoblast alkaline phosphatase. Ongoing work includes histology analysis to elucidate the mechanisms underpinning the changes seen in the bones of testosterone deficient animals

Osteoarthritis is one of the major causes of immobility. Most commonly, osteoarthritis manifests at the knee joint. Prevalence of knee osteoarthritis (KNOA) increases with age. Another important risk factor for KNOA is obesity. Research has shown that obese subjects have almost four times the risk of developing KNOA, which may be explained by both an increased knee loading. In medial compartment KNOA, the knee adduction moment (KAM) during gait is considered a marker for disease severity. KAM is dependent of the magnitude of the ground reaction force and its moment arm relative to the knee joint centre. In addition, obesity has been reported to augment KAM during gait. However, after removal of the direct contributions of body weight, KAM parameters may be different due to obesity-related gait adaptations to limit knee loading. While KAM has been thoroughly investigated during gait, little is known about KAM during stair negotiation, during which knee loads are higher compared to gait. The aim of the current study is therefore to compare normalized KAM during the stance phase of stair negotiation between lean KNOA patients, obese KNOA patients, and healthy controls. This case control study included 20 lean controls, 14 lean KNOA patients, and 16 obese KNOA patients. All subjects ascended and descended a two-step staircase at a self-selected, comfortable speed. Radiographic imaging and MRI were used to evaluate knee cartilage and KNOA status. Motion analysis was performed with a three-dimensional motion capture system. Kinetic data were obtained by one force platform. The parameters of study included: stance phase duration, toe-out angle, KAM peaks and KAM impulse. During stair ascent obese KNOA patients showed a longer stance phase than healthy controls (P 0.050). Despite high between-subject variability, KAM impulse was found 45% higher in the obese KNOA group during stair descent, when compared to healthy controls (P =0.012). The absence of a significant effect of groups on the normalized KAM during stair negotiation may be explained by a lower ambulatory speed in the obese KNOA group, that effectively lowers GRFz. Decreasing ambulatory speed may be an effective strategy to lower KAM during stair negotiation

Introduction. Curved varus intertrochanteric osteotomy of the femur is an excellent and minimally invasive method for the treatment of osteonecrosis of the femoral head or osteoarthritis of the hip for joint preservation. However, the early postoperative complications of this procedure may be due to separation at the osteotomy site and an increase in varus angle due to early partial weight bearing. Methods. We modified the curved varus intertrochanteric osteotomy of the femur by performing an additional rotation. Regarding the surgical technique, curved varus osteotomy is performed at an angle of 30 degrees to the femoral shaft and an additional rotational osteotomy is also performed at an angle of 15 or 20 degrees to the osteotomy plane. Partial weight bearing with one-third body weight is permitted 3 weeks after surgery. Results. Curved varus intertrochanteric osteotomy of the femur was designed for developmental dysplastic hip by Nishio in 1969 and reported to have good outcomes in 1971. An important feature of this method is that the incidence of high riding of the greater trochanter or shortening of leg length is less than that in varus intertrochanteric osteotomy. Moreover, good contact at the osteotomy site and less lateral shift of the femoral shaft is observed. However, we have experienced a case of separation at the osteotomy site and increase of the varus angle in our hospital. Previous reports recommended that partial weight bearing with one-third body weight should be initiated after 5 weeks and full weight bearing after 6 months because the contact area is decreased at the osteotomy site by varus osteotomy. The post-operative recovery of the patients with total hip arthroplasty is rapid, therefore, we must consider important issues such as initiating the rehabilitation program early and reducing the duration of hospitalization. As per our experience, we think that partial weight bearing with one-third body weight should be initiated at 3 weeks. At the osteotomy site, we rotated the nearest bone segment to move it such that it intersects the proximal and distal bone cortex. Therefore, the osteotomy site will be stabilized and will have the ability to endure load. Another feature of this technique is that the partial removal of the necrotic area leads to an increase in the healthy load-bearing area. A limitation of this method is that an angle of an additional rotation is up to 30 degrees, because the joint capsule cannot be incised circumferentially and the short external rotator tendons should also be preserved. Conclusion. Modified curved varus intertrochanteric osteotomy is a useful method for the prevention of increased degree of a varus angle as well as for obtaining more intact area of femoral head in osteonecrosis

The use of lumbar fusion procedures in the USA and Europe has rapidly increased over the last decade and a large number of these procedures involve the use of bone grafts. Despite of technical progress of spinal surgery and operative materials the risk of vertebral fusion failure occurs in 5 – 35 % of cases. Autografting has been considered the gold standard for bone graft procedures. However, the harvesting from the iliac crest can be associated with short and long-term morbidity in up to 22 % of cases. Main goal of this experimental study was to compare newly developed hybrid biodegradable nanocomposit porous implant (HBNPI) against bone craft from iliac crest as a new and better alternative for lumbar interbody fusion. 24 male pigs 4 months old weighting around 40 Kg were included in our study. These pigs were divided into two study groups depending on fusion method. Group A – 12 pigs underwent lateral lumbal interbody fusion (L2/3) with implantation of iliac crest bonegraft. Group B - 12 pigs underwent lateral lumbal interbody fusion (L2/3) with newly developed HBNPI. Each group were divided into two subgroups from these 6 spines were harvested 8 weeks (subgroup A1, B1) and 6 spines 16 weeks (group A2, B2) after surgery. After sacrifice, the lumbar spines were taking out and micro-CT, biomechanical testing and histomorphological analysis in all groups were performed to evaluate a quality of intervertebral fusion. As controls (group N), 6 cadaveric intact lumbar spines underwent biomechanical, micro-CT and histological testing. All 24 animals recovered from general anesthesia without unusual events. The operations lasted between 50–90 minutes (mean 70) in Group A and between 35–72 minutes (mean 43) in Group B. All of the pigs from group A could stand up and were mobile within 20 hours (range 7–20). When bone graft harvesting was not necessary (group B) this time was shortened, ranging from 1 – 1,5 hour. All pigs from Group A were limping on the first postoperative day. No limping animal was observed in group B. Total body weight of the pigs increased from 37 kg (range 36–40) at the start to 85 (range 80–89) at sacrifice. Biomechanics evaluation shows that extension flexural stiffness values are statistically significantly different between A2 (16 weeks post-implant) and A1 (8 weeks post-implant). Group A2 achieves higher values than Group A1, which is attributed to the adhesion of the implant to the surrounding vertebrae. Similarly, this also applies to groups B2 and B1. The flexural stiffness at group B2 extension is statistically significantly higher than the A2 group and also than the native N group. Biomechanical evaluation supports findings on micro-CT and histological specimens, where both adjacent vertebrae are completely fused in groups B2, unlike in group A2, where there is no or incomplete fusion. Newly developed HBNPI represents new possibility how to do intervertebral fusion, and simultaneous become chance how to improve and accelerate bone healing process against standard procedures

Hip osteoarthritis (OA) is a disorder of high socio-economic relevance. The causes of hip osteoarthritis are multifactorial; however, the epidemiological literature regularly cites occupational tasks, such as heavy lifting and carrying, as a risk factor for the development of hip OA. The level of mechanical stresses upon the hip joint caused by occupational tasks remain largely unclear, however. This project sought to quantify the levels of stresses upon the hip joint during occupational tasks. In particular we were interested in comparing load as well as stress levels from everyday activities with occupational tasks typically performed by blue collar workers. Sectors and occupational activities presenting a high potential for stress upon the hip joint were identified by means of a survey conducted among accident insurance institutions. Lifting, carrying and load transfer (25 to 50 kg), ladder climbing and stair climbing (without additional load and with an additional load of 25 kg) were selected from among these sectors and activities for the purpose of the study. Laboratory measurements were performed in which motion capturing and a range of force measurement apparatus were used to record and evaluate the performance of the selected tasks by 12 skilled workers from a number of sectors. multi-body simulation was used to calculate the stress in the form of hip-joint contact forces. The contact pressures and their geometric distribution on the cartilage surfaces of the hip joint were then calculated from these results by means of finite-element analysis. This produced an indicator for the strain upon the hip joint. The highest hip-joint forces, at (637±148)% of the body weight, occurred during handling of the 50 kg load. This corresponded to 1.7 times the stress arising during walking, at (368±78)% of the body weight. Significantly higher hip-joint forces compared to those arising during walking were observed for the carrying of loads of 40 kg and 50 kg, the handling of loads of 25 kg, 40 kg and 50 kg, and stair climbing with an additional load of 25 kg. Maximum contact pressures of 24.1 MPa were computed during the finite-element analysis (lifting of 50 kg); only very small regions of the joint surface were however affected by these high pressures. During walking, the maximum pressure reached 15 MPa. The results obtained provide a quantitative overview of the strains upon the hip joint during occupational and everyday tasks. They constitute an aid to future quantitative exposure assessments in a range of sectors and occupational fields, and thus contribute to improving estimation of the relevance of stresses of occupational origin to the incidence of hip OA