Objectives. Advanced glycation end-products (AGEs) are a post-translational modification of collagen that form spontaneously in the skeletal matrix due to the presence of reducing sugars, such as glucose. The accumulation of AGEs leads to collagen cross-linking, which adversely affects bone quality and has been shown to play a major role in fracture risk. Thus, intervening in the formation and accumulation of AGEs may be a viable means of protecting bone quality. Methods. An in vitro model was used to examine the efficacy of two AGE-inhibitors, aminoguanidine (AG) and pyridoxamine (PM), on ageing human cortical bone. Mid-diaphyseal tibial cortical bone segments were obtained from female cadavers (n = 20, age range: 57 years to 97 years) and randomly subjected to one of four treatments: control; glucose only; glucose and AG; or glucose and PM. Following treatment, each specimen underwent mechanical testing under physiological conditions via reference point indentation, and AGEs were quantified by fluorescence. Results. Treatment with AG and PM showed a significant decrease in AGE content versus control groups, as well as a significant decrease in the change in indentation distance, a reliable parameter for analyzing bone strength, via two-way analysis of variance (ANOVA) (p < 0.05). Conclusions. The data suggest that AG and PM prevent AGE formation and subsequent biomechanical degradation in vitro. Modulation of AGEs may help to identify novel therapeutic targets to mitigate bone quality deterioration, especially deterioration due to ageing and in AGE-susceptible populations (e.g. diabetics). Cite this article: O. Abar, S. Dharmar, S. Y. Tang. The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical bone. Bone Joint Res 2018;7:105–110. DOI: 10.1302/2046-3758.71.BJR-2017-0135.R1

Objectives. Platelet-rich plasma (PRP) is being used increasingly often in the clinical setting to treat tendon-related pathologies. Yet the optimal PRP preparations to promote tendon healing in different patient populations are poorly defined. Here, we sought to determine whether increasing the concentration of platelet-derived proteins within a derivative of PRP, platelet lysate (PL), enhances tenocyte proliferation and migration in vitro, and whether the mitogenic properties of PL change with donor age. Methods. Concentrated PLs from both young (< 50 years) and aged (> 50 years) donors were prepared by exposing pooled PRP to a series of freeze-thaw cycles followed by dilution in plasma, and the levels of several platelet-derived proteins were measured using multiplex immunoassay technology. Human tenocytes were cultured with PLs to simulate a clinically relevant PRP treatment range, and cell growth and migration were assessed using DNA quantitation and gap closure assays, respectively. Results. Platelet-derived protein levels increased alongside higher PL concentrations, and PLs from both age groups improved tenocyte proliferation relative to control conditions. However, PLs from aged donors yielded a dose-response relationship in tenocyte behaviour, with higher PL concentrations resulting in increased tenocyte proliferation and migration. Conversely, no significant differences in tenocyte behaviour were detected when increasing the concentration of PLs from younger donors. Conclusion. Higher PL concentrations, when prepared from the PRP of aged but not young donors, were more effective than lower PL concentrations at promoting tenocyte proliferation and migration in vitro. Cite this article: D. R. Berger, C. J. Centeno, N. J. Steinmetz. Platelet lysates from aged donors promote human tenocyte proliferation and migration in a concentration-dependent manner. Bone Joint Res 2019;8:32–40. DOI: 10.1302/2046-3758.81.BJR-2018-0164.R1

Abstract. High tibial osteotomy (HTO) is a well-recognised procedure to address medial compartment osteoarthritis (OA). There remains dispute on the impact of pre-operative patient factors on patient related outcome measures (PROMS). Does BMI and age affect > 2 year and > 5 year oxford knee scores (OKS) and Knee injury and osteoarthritis outcome scores (KOOS). A retrospective review of a prospectively collected database was performed. Timeframe was 26/6/2014 and 25/8/2022. BMI and age were recorded. OKS and KOOS were collected at > 2 years and > 5 years. There were 81 procedures included, of these 50 had OKS and KOOS scores at > 2 years and 35 at > 5 years. Median BMI was 28.5kg/m. 2. , range was 18.6–40.8kg/m. 2. Spearman's rank for >2 year OKS was p(df)=−0.210 p=0.157, > 5 year OKS p(df)=−0.215 p=0.230. For > 2 year and > 5 year KOOS subscales there were no statistically significant associations on Spearman's rank. For age, median age was 52.5, range 26–71 years old. OKS at >2 year p(df)=0.068 p=0.664, OKS >5 years p(df)=0.065 p= 0.709. For >2 year and > 5 year KOOS subscales there were no statistically significant associations on Spearman's rank. There were no adverse outcome in patients up-to the age of 71. There were no statistically significant Spearman's rank correlations between PROMS and OKS/KOOS scores. This supports recent KOG consensus statement highlighting physiological age importance vs chronological age. Of note there were more negative associations in the BMI group compared with age

Intervertebral disc (IVD) degeneration occurs with aging, leading to low back pain (LBP), which is one of the leading conditions of disability worldwide. With the lack of effective treatment, decellularized extracellular matrix (dECM) – based biomaterials have been proposed for IVD regeneration. However, the impact of donor ages on tissue repair had never been explored before in the disc field. Therefore, we aimed to address this question. For that, a decellularization protocol for bovine nucleus pulposus (NP) of different aged donors (fetus, young and old) was optimized by testing several detergents (SDS and Triton). The process efficiency was evaluated in terms of DNA and cell removal, as well as ECM preservation. Afterwards, dECMs were repopulated with bovine NP cells and cultured ex vivo. At day 7, cell behavior, ECM de novo synthesis and remodeling were evaluated [1]. Moreover, dECMs’ inflammatory response was assessed after in vivo CAM assay. Finally, inflammatory and angiogenic cytokines were analyzed in the conditioned media-derived from dECMs by using a cytokine array. As results, an optimal decellularization protocol (SDS 0.1%, 1h), efficient at removing cells and DNA from bovine NPs, while preserving ECM cues of native tissues, was developed. After repopulation, aggrecan increased in younger NPs, while collagen 2 decreased which may be indicative of matrix remodeling [1]. After in vivo CAM assay, fetal dECMs showed the highest inflammatory response. Finally, no statistically significant changes of cytokines were detected in the matrices, despite for a trend of higher IFN-α, IFN-γ and LIF in fetal dECMs, IL-1β in young dECMs and Decorin in old dECMs. Overall, this work uncovered the importance of tissue donor ages for tissue regenerative purpose, opening new avenues for the development of appropriate therapeutic strategies for IVD degeneration. Acknowledgments: FCT, EUROSPINE, ON Foundation

The use of mesenchymal stromal cells (MSCs) in regenerative medicine and tissue engineering is well established, given their properties of self-renewal and differentiation. However, several studies have shown that these properties diminish with age, and understanding the pathways involved are important to provide regenerative therapies in an ageing population. In this PRISMA systematic review, we investigated the effects of chronological donor ageing on the senescence of MSCs. We identified 3023 studies after searching four databases including PubMed, Web of Science, Cochrane, and Medline. Nine studies met the inclusion and exclusion criteria and were included in the final analyses. These studies showed an increase in the expression of p21, p53, p16, ROS, and NF- B with chronological age. This implies an activated DNA damage response (DDR), as well as increased levels of stress and inflammation in the MSCs of older donors. Additionally, highlighting the effects of an activated DDR in cells from older donors, a decrease in the expression of proliferative markers including Ki67, MAPK pathway elements, and Wnt/ -catenin pathway elements was observed. Furthermore, we found an increase in the levels of SA- -galactosidase, a specific marker of cellular senescence. Together, these findings support an association between chronological age and MSC senescence. The precise threshold for chronological age where the reported changes become significant is yet to be defined and should form the basis for further scientific investigations. The outcomes of this review should direct further investigations into reversing the biological effects of chronological age on the MSC senescence phenotype

Obesity is a known risk factor for hip osteoarthritis. The aim of this study was to compare the incidence of obesity in Australians undergoing hip replacements (HR) for osteoarthritis to the general population. A cohort study was conducted comparing data from the Australian Bureau of Statistics and the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) from 2017-18. Body mass index (BMI) data for patients undergoing primary total hip replacement and resurfacing for osteoarthritis were obtained from the AOANJRR. The distribution of HR patients by BMI category was compared to the general population, in age and sex sub-groups. During the study period, 32,495 primary HR were performed for osteoarthritis in Australia. Compared to the general population, there was a higher incidence of Class I, II, and III obesity in patients undergoing HR in both sexes aged 35 to 74 years old. Class III obese females and males undergoing HR were on average 6 to 7 years younger than their normal weight counterparts. Class III obese females and males aged 55-64 years old were 2.9 and 1.7 times more likely to undergo HR, respectively (p<0.001). There is a strong association between increased BMI and relative risk of undergoing HR. Similar findings have been noted in the United States of America, Canada, United Kingdom, Sweden and Spain. A New Zealand Registry study and recent meta-analysis have also found a concerning trend of Class III obese patients undergoing HR at a younger age. Obese Australians are at increased risk of undergoing HR at a younger age. A national approach to address the prevalence of obesity is needed

Aims. The aims of the study were to report for a cohort aged younger than 40 years: 1) indications for HRA; 2) patient-reported outcomes in terms of the modified Harris Hip Score (HHS); 3) dislocation rate; and 4) revision rate. Methods. This retrospective analysis identified 267 hips from 224 patients who underwent an hip resurfacing arthroplasty (HRA) from a single fellowship-trained surgeon using the direct lateral approach between 2007 and 2019. Inclusion criteria was minimum two-year follow-up, and age younger than 40 years. Patients were followed using a prospectively maintained institutional database. Results. A total of 217 hips (81%) were included for follow-up analysis at a mean of 3.8 years. Of the 23 females who underwent HRA, none were revised, and the median head size was 46 mm (compared to 50 mm for males). The most common indication for HRA was femoroacetabular impingement syndrome (n = 133), and avascular necrosis ( (n = 53). Mean postoperative HHS was 100 at two and five years. No dislocations occurred. A total of four hips (1.8%) required reoperation for resection of heterotopic ossification, removal of components for infection, and subsidence with loosening. The overall revision rate was 0.9%. Conclusion. For younger patients with higher functional expectations and increased lifetime risk for revision, HRA is an excellent bone preserving intervention carrying low complication rates, revision rates, and excellent patient outcomes without lifetime restrictions allowing these patients to return to activity and sport. Thus, in younger male patients with end-stage hip disease and higher demands, referral to a high-volume HRA surgeon should be considered. Cite this article: Bone Jt Open 2023;4(6):408–415

Aims. A national screening programme has existed in the UK for the diagnosis of developmental dysplasia of the hip (DDH) since 1969. However, every aspect of screening and treatment remains controversial. Screening programmes throughout the world vary enormously, and in the UK there is significant variation in screening practice and treatment pathways. We report the results of an attempt by the British Society for Children’s Orthopaedic Surgery (BSCOS) to identify a nationwide consensus for the management of DDH in order to unify treatment and suggest an approach for screening. Methods. A Delphi consensus study was performed among the membership of BSCOS. Statements were generated by a steering group regarding aspects of the management of DDH in children aged under three months, namely screening and surveillance (15 questions), the technique of ultrasound scanning (eight questions), the initiation of treatment (19 questions), care during treatment with a splint (ten questions), and on quality, governance, and research (eight questions). A two-round Delphi process was used and a consensus document was produced at the final meeting of the steering group. Results. A total of 60 statements were graded by 128 clinicians in the first round and 132 in the second round. Consensus was reached on 30 out of 60 statements in the first round and an additional 12 in the seond. This was summarized in a consensus statement and distilled into a flowchart to guide clinical practice. Conclusion. We identified agreement in an area of medicine that has a long history of controversy and varied practice. None of the areas of consensus are based on high-quality evidence. This document is thus a framework to guide clinical practice and on which high-quality clinical trials can be developed. Cite this article: Bone Joint J 2023;105-B(2):209–214

Abstract. Purpose. Unicompartmental knee arthroplasty (UKA) is an effective treatment for late knee osteoarthritis (OA). However, its indications remain controversial. Young age (< 60 years) has been associated with worse outcomes. The goal of this systematic review and meta-analysis is to study the effect of age on UKA outcomes. Methods. The primary objective was to compare the UKA revision rate in young patients with that of old patients, using the age thresholds of 60 and 55 years. Secondary objectives were patient-reported outcome measures (PROMs) and implant design. PubMed, Ovid, Web of Science, Google Scholar, and Cochrane library were searched in June 2021. This review was conducted in accordance with the PRISMA guidelines (PROSPERO registration number: CRD42021248322). Results. A total of 12 observational studies with 6,448 knees were included. A mean MINORS score of 19 was assigned to the review. The mean age of patients was 64.32 years, with follow-up ranging from 0.2 to 15 years. There was no significant difference in revision rate, incident or PROMs between young and old patients in the analysis for each age threshold. Further sub-analysis adjusting for implant type in mobile- and fixed-bearing prostheses also showed similar results between those above and under 60 and 55 years. Conclusion. Young age was not associated with a higher revision rate or lower functional scores. Thus, this review provides evidence that performing UKA at a younger age (< 60 years) should not be considered suboptimal. However, this finding should be applied in context, as other confounding factors need to be explored

Intra-Discal Vacuum Phenomenon (IDVP) represents an intradiscal nitrogen gas accumulation where a cavity opens in a supine position, lowering intra-discal pressure and generating a bubble. IDVP has been observed in up to 20% of elderly patients and reported in almost 50% of chronic LBP patients. With a highly accurate detection on CT, its significance lacks clarity and consideration within normative data. IDVP occurs with patterns of lumbar and/or lumbopelvic morphology and associated diagnoses. Over-60s population based sample of 2020 unrelated CT abdomen scans without acute spinal presentations, with sagittal reconstructions, inclusive of T12 to femoral heads, were analyzed for IDVP and pelvic incidence (PI). Subjects with diagnostic morphological associations of the lumbar spine, including previous fracture, autofusion, transitional vertebra and listhesis, were selected out and analyzed separately. Subjects were then equally grouped into low, medium and high PI. Prevalence of lumbar spine IDVP is 41.3%. 125 cases were excluded. 1603 subjects yielded 663 IDVP. This was increased in severity towards the lumbosacral junction (L1L2 9.4%, L2L3 10.9%, L3L4 13.7%, L4L5 19.9%, L5S1 28.5%) and those with low PI, while distribution was more even with high PI. 292 had positive diagnostic associations, which were more likely to occur at the level of isthmic spondylolisthesis, adjacent to a previous fracture or suprajacent to lumbosacral transitional vertebra (p<0.05). This study has identified normative values for prevalence and severity of IDVP in a normal aging population. Morphological patterns that influence the pattern of IVDP such as pelvic incidence and diagnostic associations provide novel insights to the function of the aging spine

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

The study of spinopelvic anatomy and movement has received great interest as these characteristics influence the biomechanical behavior (and outcome) following hip arthroplasty. However, to-date there is little knowledge of what “normal” is and how this varies with age. This study aims to determine how dynamic spino-pelvic characteristics change with age, with well-functioning hips and assess how these changes are influenced by the presence of hip arthritis. This is an IRB-approved, cross-sectional, cohort study; 100 volunteers (asymptomatic hips, Oxford-Hip-sore>45) [age:53 ± 17 (24-87) years-old; 51% female; BMI: 28 ± 5] and 200 patients with end-stage hip arthritis [age:56 ± 19 (16-89) years-old; 55% female; BMI:28 ± 5] were studied. All participants underwent lateral spino-pelvic radiographs in the standing and deep-seated positions to determine maximum hip and spine flexion. Parameters measured included lumbar-lordosis (LL), pelvic incidence, pelvic-tilt (PT), pelvic-femoral angles (PFA). Lumbar flexion (ΔLL), hip flexion (ΔPFA) and pelvic movement (ΔPT) were calculated. The prevalence of spinopelvic imbalance (PI–LL>10?) was determined. There were no differences in any of the spino-pelvic characteristics or movements between sexes. With advancing age, standing LL reduced and standing PT increased (no differences between groups). With advancing age, both hip (4%/decade) and lumbar (8%/decade) flexion reduced (p<0.001) (no difference between groups). ΔLL did not correlate with ΔPFA (rho=0.1). Hip arthritis was associated with a significantly reduced hip flexion (82 ±;22? vs. 90 ± 17?; p=0.003) and pelvic movements (1 ± 16? vs. 8 ± 16?; p=0.002) at all ages and increased prevalence of spinopelvic imbalance (OR:2.6; 95%CI: 1.2-5.7). With aging, the lumbar spine loses its lumbar lordosis and flexion to a greater extent that then the hip and resultantly, the hip's relative contribution to the overall sagittal movement increases. With hip arthritis, the reduced hip flexion and the necessary compensatory increased pelvic movement is a likely contributor to the development of hip-spine syndrome and of spino-pelvic imbalance

Osteoarthritis is a common articular cartilage disorder and causes a significant global disease burden. Articular cartilage has a limited capacity of repair and there is increasing interest in the use of cell-based therapies to facilitate repair including the use of Mesenchymal Stromal Cells (MSCs). There is some evidence in the literature that suggests that advancing age is associated with declining MSC function, including reduced proliferation and differentiation potential, and greater cellular apoptosis. In our study, we first performed a systematic review of the literature to determine the effects of chronological age on the in vitro properties of MSCs, and then performed a laboratory study to investigate these properties. We initially conducted a PRISMA systematic review of the literature to review the evidence base for the effects of chronological age on the in vitro properties of MSCs including cell numbers, expansion, cell surface characterization and differentiation potential. This was followed by laboratory based experiments to assess these properties. Tissue from patients undergoing total knee replacement surgery was used to isolate MSCs from the bone fragments using a method developed in our laboratory. The growth kinetics was determined by calculating the population doublings per day. Following expansion in culture, MSCs at P2 were characterised for a panel of cell surface markers using flow cytometry. The cells were positive for CD73, CD90 and CD105, and negative for CD34 and CD45. The differentiation potential of the MSCs was assessed through tri-lineage differentiation assays. Clear differences between the younger and older patients were indicated. Chronological age-related changes in MSC function have important implications on the use of these cells in clinical applications for an ageing population. The results from this study will be used to plan further work looking at the effects of chronological age on cellular senescence and identify pathways that could be targeted to potentially reverse any age-related changes

Abstract. Introduction. Little is known about employment following revision total knee arthroplasty (RTKA). This study aims to describe factors associated with returning to employment in patients of working age who underwent RTKA surgery. Methodology. We performed a retrospective assessment of all patients aged ≤65 who underwent RTKA at our NHS institution between 2006 and 2020. All indications and revision procedures were included. Pre-operative demographics, indication for surgery and Oxford Knee Scores (OKS) were recorded. Postal questionnaires were sent to patients including patient reported outcome measures and departmental questionnaire asking patients about employment status pre- and post-operatively. Results. 132 procedures were performed in 113 patients. Median follow up was 5.5 years (2.4–9.0). Mean age was 58 (5.8) and 50% (57) were male. 62 patients undergoing 74 procedures responded to postal questionnaires and were included in the study. 53% (33) were employed prior to surgery and 61% (38) returned to work at a median of 12 weeks (3–150). Of the 24 who did not return to work, 7 reported intending to return to work. Those patients who returned to work had increased pre-operative OKS (16.9 vs 13.6) and mean improvement (16.5 vs 12.4). Conclusion. This study is limited by small numbers and its observational nature. In this population the majority of patients who wished to return to work after RTKA were able to do so. This provides some reassurance when counselling patients. Prospective studies to better understand the factors that predict return to work will be important with increasing demands from surgery

The influence of patient age on functional outcomes after periacetabular osteotomy (PAO) for acetabular dysplasia remains unclear, with previous studies utilising scores developed for older, arthritic patients. The purpose of this study is to assess the influence of patient age on International Hip Outcome Tool (iHOT-12) scores, two years after PAO. Eighty-six patients (72 female, 14 male; mean age 26.9 years) who underwent PAO by a single surgeon and had completed a minimum of two years follow up were identified. Patients were categorised into three groups according to age at the time of surgery: adolescent (11–20 years; n=29), young adult (21–30 years; n=29), and mature (≥31 years; n=28). The three groups were compared with respect to baseline variables and functional outcomes (iHOT-12, EQ-5D quality of life score, University of California Los Angeles (UCLA) activity score, pain visual analogue score (VAS)). Multivariate regression was undertaken to assess for independent predictors of two-year iHOT-12 score. The adolescent group demonstrated a lower BMI (p=0.004) while the mature group had a greater American Society of Anaesthesiology (ASA) score (p=0.049). There were otherwise no significant differences in baseline variables between the three groups (all p>0.05). The three groups demonstrated significant post-operative improvements across all functional outcome measures. There were no significant differences in two-year iHOT-12, EQ-5D, UCLA score or pain VAS between the three groups (all p>0.05). Regression modelling found that patient age at the time of surgery did not have an independent effect on two-year iHOT-12 score (p=0.878). We found that patient age at the time of surgery did not influence functional outcomes two years after PAO. Our results suggest that patient age should not be considered in isolation as an indication or contraindication for PAO

Arthroscopic hip procedures have increased dramatically over the last decade as equipment and techniques have improved. Patients who require hip arthroscopy for femoroacetabular impingement on occasion require surgery on the contralateral hip. Previous studies have found that younger age of presentation and lower Charlson comorbidity index have higher risk for requiring surgery on the contralateral hip but have not found correlation to anatomic variables. The purpose of this study is to evaluate the factors that predispose a patient to requiring subsequent hip arthroscopy on the contralateral hip. This is an IRB-approved, single surgeon retrospective cohort study from an academic, tertiary referral centre. A chart review was conducted on 310 primary hip arthroscopy procedures from 2009-2020. We identified 62 cases that went on to have a hip arthroscopy on the contralateral side. The bilateral hip arthroscopy cohort was compared to unilateral cohort for sex, age, BMI, pre-op alpha angle and centre edge angle measured on AP pelvis XRay, femoral torsion, traction time, skin to skin time, Tonnis grade, intra-op labral or chondral defect. A p-value <0.05 was deemed significant. Of the 62 patients that required contralateral hip arthroscopy, the average age was 32.7 compared with 37.8 in the unilateral cohort (p = 0.01) and BMI was lower in the bilateral cohort (26.2) compared to the unilateral cohort (27.6) (p=0.04). The average alpha angle was 76.3. 0. in the bilateral compared to 66. 0. in the unilateral cohort (p = 0.01). Skin to skin time was longer in cases in which a contralateral surgery was performed (106.3 mins vs 86.4 mins) (p=0.01). Interestingly, 50 male patients required contralateral hip arthroscopy compared to 12 female patients (p=0.01). No other variables were statistically significant. In conclusion, this study does re-enforce existing literature by stating that younger patients are more likely to require contralateral hip arthroscopy. This may be due to the fact that these patients require increased range of motion from the hip joint to perform activities such as sports where as older patients may not need the same amount of range of motion to perform their activities. Significantly higher alpha angles were noted in patients requiring contralateral hip arthroscopy, which has not been shown in previous literature. This helps to explain that larger CAM deformities will likely require contralateral hip arthroscopy because these patients likely impinge more during simple activities of daily living. Contralateral hip arthroscopy is also more common in male patients who typically have a larger CAM deformity. In summary, this study will help to risk stratify patients who will likely require contralateral hip arthroscopy and should be a discussion point during pre-operative counseling. That offering early subsequent or simultaneous hip arthroscopy in young male patients with large CAMs should be offered when symptoms are mild

Aging impairs the regenerative capacity of musculoskeletal tissues and is associated with poor healing outcomes. PolgA. D257A/D257A. (PolgA) mice present a premature aging phenotype due to the accumulation of mitochondrial DNA (mtDNA) point mutations at rates 3 – 5 fold higher compared to wild type mice. Consequently, PolgA mice exhibit the premature onset of clinically-relevant musculoskeletal aging characteristics including frailty, osteo-sarcopenia, and kyphosis. I will present our recent findings on the use of PolgA mice to investigate the effects of aging on the regenerative capacity of bone. In particular, I will focus on the mechano-sensitivity of the regenerative process in aged bone environments and the opportunities it presents for clinical translation of mechanical intervention therapies

Aims. The primary aim of our study was to assess the influence of age on hip-specific outcome following total hip arthroplasty (THA). Secondary aims were to assess health-related quality of life (HRQoL) and level of activity according to age. Methods. A prospective cohort study was conducted. All patients were fitted with an Exeter stem with a 32 mm head on highly cross-linked polyethylene (X3RimFit) cemented acetabulum. Patients were recruited into three age groups: < 65 years, 65 to 74 years, and ≥ 75 years, and assessed preoperatively and at three, 12, 24, and 60 months postoperatively. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), and Hip disability and Osteoarthritis Outcome Score (HOOS), were used to assess hip-specific outcome. EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and 36-Item Short Form Survey (SF-36) scores were used to assess HRQoL. The Lower Extremity Activity Scale (LEAS) and Timed Up and Go (TUG) were used to assess level of activity. Results. There were no significant (p > 0.05) differences in the WOMAC scores, HSS, HOOS, or EQ-5D-5L at any postoperative timepoint between the age groups. Patients aged ≥ 75 years had significantly lower physical function (p ≤ 0.010) and physical role (p ≤ 0.047) SF-36 scores at 12, 24, and 60 months, but were equal to that expect of an age-matched population. No differences according to age were observed for the other six domains of the SF-36 (p > 0.060). The ≥ 75 years group had a lower LEAS (p < 0.001) and longer TUG test times (p ≤ 0.032) compared to the < 65 years group, but older age groups had significant (p < 0.001) improvement relative to their preoperative baseline measures. Conclusion. Age did not influence postoperative hip-specific outcome or HRQoL (according to the EQ-5D) following THA. Despite a significant improvement, older patients had lower postoperative activity levels compared to younger patients, but this may be reflective of the overall physical effect of ageing. Cite this article: Bone Jt Open 2022;3(9):692–700

Aims. This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. Methods. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload. Results. Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment. Conclusion. Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing. Cite this article: Bone Joint Res 2024;13(9):427–440

Abstract. Objectives. Osteoarthritis is a common articular cartilage disorder and causes a significant global disease burden. Articular cartilage has a limited capacity of repair and there is increasing interest in the use of cell-based therapies to facilitate repair including the use of Mesenchymal Stromal Cells (MSCs). There is some evidence in the literature that suggests that advancing age and gender is associated with declining MSC function, including reduced proliferation and differentiation potential, and greater cellular apoptosis. In our study, we first performed a systematic review of the literature to determine the effects of chronological age and gender on the in vitro properties of MSCs, and then performed a laboratory study to investigate these properties. Methods and Results. We initially conducted a PRISMA systematic review of the literature to review the evidence base for the effects of chronological age and gender on the in vitro properties of MSCs including cell numbers, expansion, cell surface characterization and differentiation potential. This was followed by laboratory-based experiments to assess these properties. Compare the extent of the effect of age on MSC cell marker expression, proliferation and pathways. Tissue from patients undergoing total knee replacement surgery was used to isolate MSCs from the synovium, fat pad and bone fragments using a method developed in our laboratory. The growth kinetics was determined by calculating the population doublings per day. Following expansion in culture, MSCs at P2 were characterised for a panel of cell surface markers using flow cytometry. The cells were positive for CD73, CD90 and CD105, and negative for antibody cocktail (eg included CD34, CD45). The differentiation potential of the MSCs was assessed through tri-lineage differentiation assays. At P2 after extracting RNA, we investigate the gene analysis using Bulk seq. Clear differences between the younger and older patients and gender were indicated. Conclusions. Chronological age and gender-related changes in MSC function have important implications on the use of these cells in clinical applications for an ageing population. The results from this study will be used to plan further work looking at the effects of chronological age and gender on cellular senescence and identify pathways that could be targeted to potentially reverse any age and gender-related changes. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project