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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 141 - 141
4 Apr 2023
Timmen M Arras C Roters N Kronenberg D Bixel M Adams R Stange R
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Neoangiogenesis drives the replacement of mineralised cartilage by trabecular bone during bone growth regulated by molecules like e.g. VEGF, OPG and RANKL. The Heparan sulfate proteoglycan Syndecan-1 (Sdc1) plays a role in the interaction of osteoclasts and osteoblasts and the development of blood vessels. We expected Sdc1 to have an influence on bone structure and vessel development. Therefore, bone structure and angiogenesis at the growth plate in mice was compared and the influence of Syndecan-1 deficiency was characterised. Animals: Femura of male and female C57BL/6 WT (5♀, 6♂) and Sdc1-/- (9♀, 5♂) mice were used for native bone analysis at 4 month age. Histology: Bone structure was analysed using microCT scans with a resolution of 9µm. Vascularisation was visualised using an anti-Endomucin antibody in 80µm thick cryosections. In vitro angiogenesis: Bone marrow isolates were used to generate endothelial progenitor cells by sequential cultivation on fibronectin. Microvessel development was analysed 4h after plating on matrigel. Bone structure in male Sdc1 deficient mice was significantly reduced compare to male WT, whereas female mice of both genotypes did not differ. Sdc1 deficient mice at the age of 4 month showed a high decrease in the number of vessel bulbs at the chondro-osseous border (growth plate) compared to WT mice. However, no sex related differences were shown. Quantification of microvessel outgrowth of endothelial cells revealed a decreased amount of sprouting, but increased length of microvessels of Sdc1-/- cells compared to WT. Syndecan-1 has a significant impact on neoangiogenesis at the chondro-osseous border of the native bone, but the impact of Syndecan-1 deficiency on the loss of bone structure was significantly higher in male mice. This emphasises the importance to further characterise the function of Syndecan-1 regulated processes during enchondral ossification in a sex dependent manner


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_14 | Pages 31 - 31
1 Nov 2018
Mason R
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There is a growing requirement by governmental and other funders of research, that investigators pay attention to and integrate considerations of sex and gender in their health research studies. Doing so, the argument goes, will reduce data waste, lead to the generation of more complete and accurate evidence to apply to the delivery of health care, and hopefully improve outcomes for both male and female patients. Yet, it is not always clear what sex and gender mean and how best to apply these to the study of diverse health conditions and health service delivery. In this presentation sex, gender and other related factors will be considered in the context of fractures, fracture repair, and post-operative management. Examples of sex and gender bias, sex and gender differences, and the integration of sex and gender in research on fracture and fracture repair will be presented


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_14 | Pages 32 - 32
1 Nov 2018
Hoang-Kim A
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We need to shift our focus to integrating sex and gender into research proposals, so we can answer some of the most basic unanswered questions in the field of fracture management. Current evidence in guidelines indicate a near-to-linear increase from the 1990s for inclusion of sex and gender. However, these recommendations remain expressed in absolute terms, with little explanatory power, affecting uptake and implementation in clinical practice. This co-branded session, with members of the Orthopaedic Research Society – International section of fracture repair (ORS-ISFR), will provide participants with guiding principles and tools to assist researchers and grant reviewers understand what it means to include sex and gender in meaningful ways: from formulating research questions, recruitment strategies, to conducting sex-stratified analyses. In this presentation, we will consider diverse approaches, methods and, analyses to elevate sex and gender within trauma. A strong emphasis on the ways and means of including marginalized and vulnerable populations in research will be addressed


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 9 | Pages 1278 - 1284
1 Sep 2005
Irie T Aizawa T Kokubun S

Sex hormones play important roles in the regulation of the proliferation, maturation and death of chondrocytes in the epiphyseal growth plate. We have investigated the effects of male castration on the cell kinetics of chondrocytes as defined by the numbers of proliferating and dying cells. The growth plates of normal rabbits and animals castrated at eight weeks of age were obtained at 10, 15, 20 and 25 weeks of age. Our study suggested that castration led to an increase in apoptosis and a decrease in the proliferation of chondrocytes in the growth plate. In addition, the number of chondrocytes in the castrated rabbits was less than that of normal animals of the same age


We aim to analyze the role of patient-related factors on the yield of progenitor cells in the bone marrow aspiration concentrate (BMAC). We performed a retrospective analysis of patients who underwent autologous iliac crest-based BMAC therapy between Jan 2021–and June 2021. Patient-related factors such as age, sex, and comorbidities and procedure variables such as aspirate volume were analyzed. The yield of the bone marrow aspiration concentrate was assessed with MNC count and CFU assay from the aspirates. 63 patients with a mean age of 51.33±17.98 years were included in the study. There were 31 males and 32 females in the study population with a mean volume of 67.16±17.312 ml being aspirated from the iliac crest for the preparation of BMAC. The final aspirate had a mean MNC count of 20.16±15.73×10^6 cells which yielded a mean of 11±12 CFUs. We noted significant negative correlation between age and MNC count (r=minus;0.671, p<0.001) and CFUs (r=minus;0.688, p<0.001). We did not find the sex to have any significant role in MNC (p=0.082) count or CFUs formed (p=0.348). The presence of comorbidity significantly reduced the MNC count (p=0.003) and CFUs formed (p=0.005). The aspiration volume significantly negatively correlated with MNC count (r=minus;0.731, p<0.001) and CFUs (r=minus;0.618, p<0.001). The MNC count and CFUs formed from the BMAC depend on the patient-specific subjective variables such as age, and comorbid conditions present in them. Sex and volume of aspiration do not alter the MNC count or the CFUs formed from BMAC


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 117 - 117
14 Nov 2024
Tirta M Rahbek O Kold S Husum HC
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Introduction. Selective screening of children at risk for developmental dysplasia of the hip (DDH) is based on clinical examination and risk factor identification. Two meta-analyses published in 2012 found breech presentation, family history of DDH, female sex and primiparity to increase the risk of DDH. However, the DDH definition, reference tests and age of the examined children vary considerably, complicating the translation of those findings to current screening guidelines. The aim of this meta-analysis was to evaluate the association of previously proposed risk factors to the risk of sonographically verified DDH. Method. We searched PubMed, EMBASE and Cochrane library to identify cohort, RCTs, case-control and cross-sectional studies from 1980 to 2023 in English language. Eligible studies included participants under three months of age, where the diagnosis of DDH was made by hip ultrasound using the gold standard Graf method and reported information on one or more of the proposed risk factors and final diagnosis was available. Result. Of 5363 studies screened, 20 studies (n=64543 children) were included. Breech presentation (OR: 4.2, 95%CI 2.6-6.6), family history (3.8, 95%CI 2.1-7.2), female sex (2.5, 95%CI 1.7-3.6), oligohydramnios (3.8, 95%CI 1.7-8.5) and high birthweight (2.0, 95%CI 1.6-2.5) significantly increased the risk of DDH. C-section, primiparity, multiple births, low birthweight and prematurity were not found to increase the risk for DDH, and there was only one study about clubfoot as a risk factor. Heterogeneity was high (I. 2. >75%) in all the tested factors except high birthweight (I. 2. =0%). Subgroup analysis was performed to investigate these heterogeneities. Conclusion. Family history of DDH and breech presentation are associated with significant increase of the risk of sonographic DDH in children aged three months. A similar risk increase was detected for oligohydramnios, which was not detected in previous meta-analyses. Additionally, the DDH risk increase of female sex was found to be lower than previously reported


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 23 - 23
2 Jan 2024
Ciatti C Quattrini F Asti C Maniscalco P
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Previous scientific studies have highlighted how coupling is an important element affecting total hip arthroplasty's survival. This study aims to evaluate whether metal-on-metal (MOM) coupling could be a statistically significant risk factor. The data from the regional joint registry (Registro dell'Impiantologia Protesica Ortopedica, RIPO) was used for analysis. The data collection accuracy of this registry was 97.2% in 2017. We retrospective evaluate all MOM total hip arthroplasties (THAs) implanted in our department between January 01st 2000 and December 31st 2011. We used a control group composed by all other prosthesis implanted in our Department in the same time lapse. We registered 660 MOM THAs. Mean age of patients was 66.9 years. 603 patients have a >36mm head, while 78 a <36 mm one. Neck modularity was present in half of patients. 676 implants were cementless. We registered 69 revisions, especially due to aseptic mobilization (16 THAs), implant breakage (9 THAs) and periprosthetic fracture (6 THAs). The MOM THAs overall Kaplan-Meier survival rate was 87.2 at 15 years, and the difference between MOM THAs and other implants two curves is statistically significant (p<0.05). Male sex is a significant risk factors. Further evaluations are in progress to establish the presence of any additional risk factors. We think weight and/or BMI may be included in this category. Our study confirms the data currently present in the literature regarding a lower survival of metal-on-metal hip prostheses. The male sex is a statistically significant risk factor (p<0.05), while age, head size and modularity of the prosthetic neck are not statistically significant (p>0.05). Any new finds will be presented at the congress venue


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 76 - 76
14 Nov 2024
Yasuda T Ota S Mitsuzawa S Yamashita S Tsukamoto Y Takeuchi H Onishi E
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Introduction. A recent study to identify clinically meaningful benchmarks for gait improvement after total hip replacement (THA) has shown that the minimum clinically important improvement (MCII) in gait speed after THA is 0.32 m/sec. Currently, it remains to be investigated what preoperative factors link to suboptimal recovery of gait function after THA. This study aimed to identify preoperative lower-limb muscle predictors for gait speed improvement after THA for hip osteoarthritis. Method. This study enrolled 58 patients who underwent unilateral primary THA. Gait speed improvement was evaluated as the subtraction of preoperative speed from postoperative speed at 6 months after THA. Preoperative muscle composition of the glutei medius and minimus (Gmed+min) and the gluteus maximus (Gmax) was evaluated on a single axial computed tomography slice at the bottom end of the sacroiliac joint. Cross-sectional area ratio of individual composition to the total muscle was calculated. Result. The females (n=45) showed smaller total cross-sectional areas of the gluteal muscles than the males (n=13). Gmax in the females showed lower lean muscle mass area (LMM) and higher ratios of the intramuscular fat area and the intramuscular adipose tissue area to the total muscle area (TM) than that in the males. Regression analysis revealed that LMM/TM of Gmed+min may correlate negatively with postoperative improvement in gait speed. Receiver operating characteristic curve analysis for prediction of MCII in gait speed at ≥ 0.32 m/sec resulted in the highest area under the curve for Gmax TM with negative correlation. The explanatory variables of hip abductor muscle composition predicted gait speed improvement after THA more precisely in the females compared with the total group of both sexes. Conclusion. Preoperative Gmax TM could predict gait speed MCII after THA. Preoperative muscle composition should be evaluated separately based on sexes for achievement of clinically important improvement in gait speed after THA


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 1 - 1
17 Apr 2023
Sgardelis P Giddins G
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Distal radius fractures are common, particularly in post-menopausal women. Several factors have been identified such as osteopenia and an increased risk of falling. We hypothesised that increased soft tissue padding from muscle and fat in the volar hand may confer an element of protection against fractures more in men than women and more in younger than older patients. The aim of the study was to assess for thenar and hypothenar thickness and assess whether it varies between sexes and changes with age. We retrospectively evaluated hand MRI scans performed for non-acute conditions in adults without previous injury or surgery. Using the Patient Archiving and Communication System (PACS) we measured the distance (mm) from the volar surface of the trapezium to the skin, the hook of the hamate to skin and the pisiform to skin as measures of thenar and hypothenar thickness. We also recorded the sex and age of the subjects. Soft tissue thickness was corrected for hand size by dividing by capitate length which we measured; we have already established this as a surrogate measure of hand size. The scans of 51 men (mean age 35, range 19–66) years and 27 women (mean age 49, range 19–79) years were reviewed. Men had significantly thicker soft tissues compared to women over both the thenar and hypothenar eminences (p=0.0001). Soft tissue thickness did not change significantly with age (p> 0.05). The study confirms a significant difference in volar hand soft tissue thickness between men and women accounting for differences in hand size. Our previous research has shown how we fall onto our outstretched hands in the upper limb falling reflex and we have shown that padding the thenar and hypothenar eminences reduces force transmission to the forearm bones. In theory thicker thenar and hypothenar musculature would help protect against distal radius fractures following a fall on an outstretched hand. The thinner musculature on women may further predispose them to an increased risk of distal radius fractures. Further research is needed to assess for any loss of volar hand soft tissue thickness beyond age 75 years


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 29 - 29
11 Apr 2023
Boljanovic D Razmjou H
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The purpose of the this survey study was twofold: 1) to examine different aspects of satisfaction with post-operative care in injured workers who have undergone rotator cuff surgery and 2) to examine the relationship between receiving a newly implemented summary report and the overall satisfaction with surgery and recovery. The clinical communication summary report was given to injured workers following their review assessment to share with the family doctor or other health care providers. The form indicated a need for further assessments or investigations and return to work recommendations. The study involved using a satisfaction survey that examined different aspects of follow-up visit and workers’ opinion about their understanding of the nature of surgery, their progress, clinical management, and usefulness of the newly implemented summery report. Eighty patients completed the questionnaire (mean age: 54 (8), 62(78%) males, of whom 26 (34%) had a rotator cuff decompression and 31 (40%) had a rotator cuff repair with 20 (26%) having both procedures and three missing data. There were no statistically significant relationships between the patient demographics (age, sex or type of surgery) and satisfaction. However, there was a significant correlation between how patients perceived the summary report in terms of helpfulness and the overall satisfaction with surgery (FTE<0.0004, p=0.001) and the satisfaction with recovery (FTE<0.0001, p=0.001). This may indicate that improvement in worker's understanding of their treatment recommendations and restrictions is associated with higher levels of overall satisfaction in this population. Our results indicate a positive linear relationship between expressing a high satisfaction and the helpfulness of the summary report. As part of improving care, adding a summary report may facilitate sharing information with the injured workers, their care providers and their workplace


Introduction. Orthopedics is experiencing a significant transformation with the introduction of technologies such as robotics and apps. These, integrated into the post-operative rehabilitation process, promise to improve clinical outcomes, patient satisfaction, and the overall efficiency of the healthcare system. This study examines the impact of an app called Mymobility and intra-operative data collected via the ROSA® robotic system on the functional recovery of patients undergoing robot-assisted knee arthroplasty. Method. The study was conducted at a single center from 2020 to 2023. Data from 436 patients were included, divided into “active” patients (active users of Mymobility) and “non-active” patients. Clinical analyses and satisfaction surveys were carried out on active patients. The intra-operative parameters recorded by ROSA® were correlated with the Patient-Reported Outcome Measures (PROMs) collected via Mymobility. Result. Intra-operative data showed significant correlations with PROMs for the 48 active patients, highlighting the importance of parameters such as medial joint space and ligament laxity. No significant differences were observed between the sexes, but a positive correlation was detected between age and PROMs. The data analysis indicated that an increased medial joint space and reduced ligament laxity are associated with better PROMs. The adoption of Mymobility remained limited, with only 10% of patients fully utilizing the app. Critical factors have been identified to improve recruitment, engagement, and overall experience with the platform. Conclusion. The integration of technologies such as Mymobility and ROSA® in post-operative rehabilitation offers numerous advantages, including the objectification of data, active patient involvement, and personalized care. Challenges remain related to costs, patient compliance, and demographic limitations. Nevertheless, these technologies represent a milestone in modern peri-operative management, being able to improve clinical outcomes and the quality of care


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 13 - 13
17 Apr 2023
Andreani L Vozzi G Petrini M Di Stefano R Trincavelli M Mani O Olivieri M Bizzocchi F Creati G Capanna R
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Traumatic acute or chronic tendon injuries are a wide clinical problem in modern society, resulting in important economic burden to the health system and poor quality of life in patients. Due to the low cellularity and vascularity of tendon tissue the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Tissue engineering and regenerative medicine are promising alternatives to the natural healing process for tendon repair, especially in the reconstruction of large damaged tissues. The aim of TRITONE project is to develop a smart, bioactive implantable 3D printed scaffold, able to reproduce the structural and functional properties of human tendon, using FDA approved materials and starting from MSC and their precursor, MPC cell mixtures from human donors. Total cohort selected in the last 12 months was divided in group 1 (N=20) of subjects with tendon injury and group 2 (N=20) of healthy subject. Groups were profiled and age and gender matched. Inclusion criteria were age>18 years and presence of informed consent. Ongoing pregnancy, antihypertensive treatment, cardiovascular diseases, ongoing treatment with anti-aggregants, acetylsalicylic-acid or lithium and age<18 years were exclusion criteria. Firstly, we defined clinical, biological, nutritional life style and genetic profile of the cohort. The deficiency of certain nutrients and sex hormonal differences were correlated with tendon-injured patients. It was established the optimal amount of MPC/MSC human cell (collected from different patients during femoral neck osteotomy). Finally, most suitable biomaterials for tendon regeneration and polymer tendon-like structure were identified. Hyaluronic acid, chemical surface and soft-molecular imprinting (SOFT-MI) was used to functionalize the scaffold. These preliminary results are promising. It will be necessary to enroll many more patients to identify genetic status connected with the onset of tendinopathy. The functional and structural characterization of smart bioactive tendon in dynamic environment will represent the next project step


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 45 - 45
4 Apr 2023
Knopp B Harris M
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This study was conducted to investigate the characteristics, complications, radiologic features and clinical course of patients undergoing reduction of forearm fractures in order to better inform patient prognosis and postoperative management. We conducted a retrospective cohort study of 1079 pediatric patients treated for forearm fractures between January 2014 and September 2021 in a 327 bed regional medical center. A preoperative radiological assessment and chart review was performed. Percent fracture displacement, location, orientation, comonution, fracture line visibility and angle of angulation were determined by AP and lateral radiographs. Percent fracture displacement was derived by: (Displacement of Bone Shafts / Diameter) x 100% = %Fracture Displacement. Angle of angulation and percent fracture displacement were calculated by averaging AP and lateral radiograph measurements. 80 cases, averaging 13.5±8.3 years, were identified as having a complete fracture of the radius and/or ulna with 69 receiving closed reduction and 11 receiving fixation via an intramedullary device or percutaneous pinning. Eight patients (10%) experienced complications with four resulting in a refracture and four resulting in significant loss of reduction (LOR) without refracture. Fractures in the proximal ⅔s of the radius were associated with a significant increase in complications compared to fractures in the distal ⅓ of the radius (31.6% vs 3.4%) (P=.000428). Likewise, a higher percent fracture displacement was associated with a decreased risk of complications (28.7% vs 5.9% displacement)(P=0.0403). No elevated risk of complications was found based on fracture orientation, angulation, fracture line visibility, forearm bone(s) fractured, sex, age or arm affected. Our result highlights radius fracture location and percent fracture displacement as markers with prognostic value following forearm fracture. These measurements are simply calculated via pre-reduction radiographs, providing an efficient method of informing risk of complications following forearm fracture


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 44 - 44
14 Nov 2024
Sohn R Assar T Kaufhold I Brenneis M Braun S Junker M Zaucke F Pongratz G Jenei-Lanzl Z
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Introduction. Recent studies suggested that the progression of osteoarthritis (OA), a chronic degenerative joint disease, may be affected by the autonomic nervous system (ANS). Under healthy conditions, the sympathetic (SNS) and parasympathetic (PNS) branches of the ANS are well coordinated to maintain homeostasis. However, pathological conditions are frequently associated with a disturbance of this fine-tuned balance. Therefore, we analyzed whether an autonomic dysfunction occurs in OA patients. Method. 225 participants with early- or late-stage knee OA as well as 40 healthy age-matched probands were included in this study. Autonomic activity was investigated by analyzing heart rate variability (HRV), which decreases under chronic sympathetic overactivity. Time- and frequency-domain HRV indices SDRR, RMSSD, pRR50 and LF were examined. Linear regression analysis was performed to adjust for clinical characteristics, such as age, sex, BMI, or medication. Moreover, perceived chronic stress (PSQ) and pain (WOMAC) were assessed via questionnaires. In addition, the serum stress hormones cortisol, DHEA-S and IL-6 were analyzed via ELISA. Result. SDRR, RMSSD, and pRR50 were slightly reduced in the early stage of OA and showed significant decrease in the later stage of the disease. Also LF decreased significantly with OA progression. HRV was significantly influenced by the grade of OA, but not other patient characteristics. Moreover, late-stage OA patients demonstrated significantly higher PSQ and WOMAC levels compared to healthy controls. In addition, cortisol/DHEA-S ratio and IL-6 serum concentrations were significantly higher in late-stage than in early-stage OA patients and healthy controls. Conclusion. Reduced HRV, increased cortisol/DHEA-S ratio and PSQ level as well as elevated systemic IL-6 concentration indicated an autonomic shift towards a more pronounced SNS activity due to PNS deficiency in OA patients, particularly in the late-stage of the disease. Therefore, modulation of the ANS, for example by vagus nerve stimulation, might be a potential treatment strategy for of knee OA patients


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 118 - 118
14 Nov 2024
Schlauch A Shah I Crawford B Martin A Denisov A Tamer P Farrell B
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Introduction. Distal femur fractures around a total knee arthroplasty (TKA) are a growing problem for orthopaedic surgeons. The purpose of this study was to identify risks of reoperation for nonunion following open reduction and internal fixation of TKA periprosthetic distal femur fractures (PDFF). Method. Patients with PDFF (AO 33A-C[VB1, C1, D1], Su types 1-3) managed operatively with open reduction and internal fixation (ORIF) were retrospectively reviewed. Exclusion criteria were acute management with a distal femur replacement, less than 6 months of follow-up, and lack of injury or follow-up radiographs. The primary outcome measure was reoperation to achieve bony union. Comparisons were made between cases that did and did not require a reoperation to achieve union. Univariate analysis was used to identify factors to be analyzed in multivariate analysis to determine independent risk factors for the primary outcome. Result. A total of 77 patients met inclusion criteria. Union rate was 69/77 (89.6%). There were no differences between the groups for age, sex, BMI, comorbidities, Su classification, open injury, or mechanism of injury. Multivariate analysis identified risks for nonunion including post-operative malalignment (OR 1.41; CI 1.20-1.64; p<0.001), notching pre-operatively (OR 1.22; CI 1.04-1.42; p=0.012), presence of screws through fracture line (OR 1.28; CI 1.17-1.39; p<0.001), plate length <12 holes (OR 1.16; CI 1.02-1.33; p=0.024) and screw density greater than 0.4 (OR 2.18; CI 1.25-3.78; p=0.006). Conclusion. The reoperation rate to promote union was 10.4%. The study identified post-operative malalignment, notching pre-operatively, presence of screws through fracture line, plate length <12 holes, and proximal screw density greater than 40% as independent risk factors for nonunion


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 116 - 116
11 Apr 2023
Buettmann E DeNapoli R Abraham L Denisco J Lorenz M Friedman M Donahue H
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Patients with bone and muscle weakness from disuse have higher risk of fracture and worse post-injury mortality rates. The goal of this current study was to better inform post-fracture rehabilitation strategies by investigating if physical remobilization following disuse by hindlimb unloading improves osteochondral callus formation compared to continued disuse by hindlimb suspension (HLS). We hypothesized that continued HLS would impair callus bone and cartilage formation and that physical rehabilitation after HLS would increase callus properties. All animal procedures were approved by the VCU IACUC. Skeletally mature, male and female C57BL/6J mice (18 weeks) underwent HLS for 3 weeks. Mice then had their right femur fractured by open surgical dissection (stabilized with 24-gauge pin). Mice were then either randomly assigned to continued HLS or allow normal physical weight-bearing remobilization (HLS + R). Mice allowed normal cage activity throughout the experiment served as controls (GC). All mice were sacrificed 14-days following fracture with 4-8 mice (male and female) per treatment. Data analyzed by respective ANOVA with Tukey post-hoc (*p< 0.05; # p < 0.10). Male and female mice showed conserved and significant decreases in hindlimb callus bone formation from continued HLS versus HLS + R. Combining treatment groups regardless of mouse sex, histological analyses using staining on these same calluses demonstrated that HLS resulted in trends toward decreased cartilage cross-sectional area and increased osteoclast density in woven bone versus physically rehabilitated mice. In support of our hypothesis, physical remobilization increases callus bone formation following fracture compared to continued disuse potentially due to increased endochondral ossification and decreased bone resorption. In all, partial weight-bearing exercise immediately following fracture may improve callus healing compared to delayed rehabilitation regimens that are frequently used


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 70 - 70
2 Jan 2024
Ely E Collins K Lenz K Paradi S Liedtke W Chen Y Guilak F
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Osteoarthritis (OA) is the leading cause of pain and disability worldwide and is characterized by the degenerative changes of articular cartilage. Joint loading is required for cartilage maintenance; however, hyper-physiologic loading is a risk factor for OA. Mechanosensitive ion channels Piezo1 and Piezo2 synergistically transduce hyper-physiologic compression of chondrocytes, leading to chondrocyte death and onset of OA. This injury response is inhibited by Piezo channel loss of function, however the mechanistic role of Piezo channels in vivo is unknown. We examined the hypothesis that deletion of Piezo in chondrocytes will protect mice from joint damage and pain-related behaviors following a surgical destabilization of the medial meniscus (DMM), investigating a key mechanistic and mechanobiological role of these channels in the pathogenesis of OA. Aggrecan-Cre Piezo1 and Piezo1/2 knockout mice ((Agc)1-CRE. ERT2. ;Piezo1. fl/fl. Piezo2. fl/fl. ) were generated and given a 5-day Tamoxifen regimen at 12-weeks of age (n=6–12/group/sex). Cre-negative mice served as controls. At 16-weeks, mice received DMM surgery on the left knee. 12-weeks following DMM prior to sacrifice, activity and hyperalgesia were measured using spontaneous running wheels and a small animal algometer. Structural changes in bone, cartilage, and synovium were characterized using microCT, histology, and Modified Mankin Score criteria. Knockout of Piezo1/2 channels was chondroprotective in both sexes following DMM surgery as demonstrated by reduced Modified Mankin Score compared to control animals. Piezo1 KO was chondroprotective in only female mice, indicating a sexually dimorphic response. Piezo1 and Piezo1/2 KO was protective against pain in male mice, while females displayed no differences compared to controls. No changes were observed in bone morphology. Chondrocyte-specific Piezo1/2 knockout protects the knee joint from structural damage, hyperalgesia and functional deficits in a surgical model of PTOA in male and female mice, illustrating the importance of Piezo channels in response to injury in vivo. Future work aims to interrogate potential sexually dimorphic responses to cartilage damage and investigating Piezo2 KO mice


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 18 - 18
14 Nov 2024
Rau Y Amtsfeld J Reimers N Behrends L Hinz N Schulz AP
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Introduction. Hip fractures, with a global age-standardised incidence rate (per 100,000 population) of 187.2 (2019), are a major public health problem. With a 7.71 billion population worldwide in 2019, hip fractures, in general, are affecting around 14.43 million people per year globally. We aim to provide a nationwide epidemiological analysis of trochanteric fractures and their respective surgical treatments. In this study we research the epidemiology of trochanteric and subtrochanteric fractures, as well as their most common kinds of osteosynthesis, on a nationwide scale in Germany. Method. Data was retrieved from the national database of the German Ministry of Interior. ICD-10-GM and OPS-data from the period of 2006-2020 were analyzed, all patients with trochanteric/subtrochanteric fractures were included. Patients were grouped by age/gender and linear-regression was performed to calculate statistically significant correlations between variables/incidences. Result. 985,104 trochanteric and 178,810 subtrochanteric-fractures were reported during the analyzed period. This calculates to a mean incidence of 80.08±6.34 for pertrochanteric and 14.53±1.50 for subtrochanteric fractures per-million-inhabitants. In both fracture-types, a distinct dependence of incidence on age can be seen. Incidence rates equally rise in both sexes through the age groups with an increase of about 288-fold from those under 60 to those over the age of 90 in pertrochanteric fractures. Intramedullary nailing was the most common kind of treatment for both fracture types with augmentative cerclages on the rise throughout the whole period. Dynamic compression screws were decreasing in frequency. Conclusion. We found an ongoing increase of incidence among the elderly and an increase in intramedullary nailing as well as augmentative cerclages. Not only could we show an age-dependence of the incidences, but also a sex-dependence that seems to remain consistent in its development. While younger males (<60 years) are at a higher risk than their female peers, older females are at significantly higher risk than their male peers


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 95 - 95
1 Nov 2021
Timmen M Husmann N Wistube J Stange R
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Introduction and Objective. Klinefelter Syndrome (KS, karyotype 47,XXY) is the most frequent chromosomal aneuploidy in males, as well as the most common cause of infertility in men. Patients suffer from a lack of testosterone, i.e. hypergonadotropic hypogonadism provoking infertility, but KS men also show an increased predisposition to osteoporosis and a higher risk of bone fracture. In a mouse model for human KS, bone analysis of adult mice revealed a decrease in bone mass that could not be rescued by testosterone replacement, suggesting a gene dosage effect originating from the supernumerary X-chromosome on bone metabolism. Usually, X chromosome inactivation (XCI) compensates for the dosage imbalance of X-chromosomal genes between sexes. Some studies suggested that expression of genes that escape silencing of the supernumerary X-chromosome (e.g. androgen receptor) has an impact on sex differences, but may also cause pathological changes in males. As a promising new such candidate for a musculoskeletal escape gene, we identified the integral membrane protein (ITM) 2a, which is encoded on the X-chromosome and related to enchondral ossification. The aim of the project was to characterize systemic bone loss in the course of aging in our KS mouse model, and whether the supernumerary X-chromosome causes differences in expression of genes related to bone development. Materials and Methods. Bone structure of 24 month (=aged) old male wild type (WT) and 41, XXY mice (B6Ei.Lt-Y) were analysed by μCT. Afterwards bones were paraffin embedded and cut. In addition, tissue of brain, liver, kidney, lung and heart were also isolated and embedded for IHC staining. Using an anti-ITM2a antibody, expression and cellular localization of ITM2a was evaluated. IHC was also performed on musculoskeletal tissue of WT embryos (E18.5) and neonatal mice to determine possible age-related differences. Results. In 24 month old mice, the analysis of the lumbar vertebrae revealed a significantly lower BV/TV, trabecular bone volume and trabecular number in the XXY- group compared to WT. Trabecular thickness appeared lower but did not reach significance, with the cortical thickness being significantly higher in the XXY- group. High expression of ITM2a was detected in bone slices of both karyotypes in the chondrocytes inside the growth plate, as well as in megakaryocytes and leucocytes as well as endothelial cells of blood vessels inside the bone marrow. Osteocytes, along with erythrocytes and erythropoetic stem cells were negative for ITM2a. Other organs that showed ITM2a positive staining were kidney (blood vessels), heart (muscle) and brain (different structures). Liver and lung tissue were negative for ITM2a. No obvious difference in the intensity of the ITM2a-expression was observed between the WT and the XXY-karyotype. Analyses of embryotic bone tissue (WT) showed high expression of ITM2a in proliferating, hypertrophic and resting chondrocytes in the growth plates of tibia and femur. In comparison, the neonatal animals (WT) did not show any protein-expression in chondrocytes. Furthermore, within the metaphysis of both, embryotic and neonatal bones, endothelial cells and osteoblasts were ITM2a-positive. Further analyses of bones and tissues from young mice (4–6 month) are ongoing. Conclusions. Bone analyses revealed a significant reduction in trabecular bone mass along with fewer and thinner trabeculae in XXY mice compared to the WT, especially in the spine. ITM2a expression was visible in different cell types inside the bone, and in addition, different expression patterns at different stages of development (embryonic/neonatal) were observed. However, we have not found a significant difference in the quantity of ITM2a between tissues of XXY-karyotypes and WT. Further analyses of X-chromosomal encoded and therefore dysregulated modulators in XXY-karyotype mice and patients may reveal new sex chromosomal effector proteins in bone metabolism


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 3 - 3
2 Jan 2024
Sohn R Assar T Braun S Brenneis M Kaufhold I Zaucke F Pongratz G Jenei-Lanzl Z
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Osteoarthritis (OA) is the most common degenerative joint disorder. Its multifactorial etiology includes age, sex, joint overloading, genetic or nervous influences. In particular, the autonomic nervous system is increasingly gaining in importance. Its two branches, the sympathetic (SNS) and parasympathetic nervous system, are well-balanced under healthy conditions. OA patients seem to be prone to an autonomic imbalance and therefore, we analyzed their autonomic status. More than 200 participants including patients with early and late stage knee OA (before and 1 year after knee replacement surgery) and healthy probands (age-matched) were analyzed. Heart rate variability was measured via electrocardiogram to assess long-term sympathetic (low-frequency=LF) and parasympathetic (high-frequency=HF, pRR50) activities or general variability (RMSSD, SDRR). Serum cortisol concentrations were measured by ELISA. Perceived chronic stress (PSQ) was assessed via questionnaire. Multivariant regression was performed for data analysis. LF/HF value of early OA was slightly increased compared to healthy controls but significantly higher compared to late OA patients before (p>0.05) and after TKR (p>0.01). HF in late OA patients before TKR was significantly decreased compared to patients after TKR (p>0.001) or healthy controls (p>0.05). Healthy probands exhibited the highest SDRR values, early OA patients had slightly lower levels and late OA patients before TKR displayed significantly reduced SDRR (p>0.001). The same differences were observed in pRR50 and RMSSD. Serum cortisol concentrations and PSQ scores increased in late OA patients before TKR. At the time point of TKR, women with beta blocker medication had significantly higher age (71 ± 9 years) than those without (63 ± 12 years)(p>0.01). An autonomic dysfunction with sympathetic dominance occurs in OA patients. The fact that beta blocker medication in women delayed the need of TKR indicates that SNS inhibition might counteract OA. Future therapeutic interventions for OA should consider a systemic approach with special regard on the ANS