Aims. To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities. Methods. We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head and the intertrochanteric region of patients with idiopathic ONFH, or from the intertrochanteric region of patients with osteoarthritis (OA), and compared their viability, mineralization capacity, and secretion of paracrine factors. Results. Osteoblasts from the intertrochanteric region of patients with ONFH showed lower alkaline phosphatase (ALP) activity and mineralization capacity than osteoblasts from the same skeletal site in age-matched patients with OA, as well as lower messenger RNA (mRNA) levels of genes encoding osteocalcin and bone sialoprotein and higher osteopontin expression. In addition, osteoblasts from patients with ONFH secreted lower osteoprotegerin (OPG) levels than those from patients with OA, resulting in a higher receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) ligand (RANKL)-to-OPG ratio. In patients with ONFH, osteoblasts from the femoral head showed reduced viability and mineralized nodule formation compared with osteoblasts from the intertrochanteric region. Notably, the secretion of the pro-resorptive factors interleukin-6 and prostaglandin E. 2. as well as the RANKL-to-OPG ratio were markedly higher in osteoblast cultures from the femoral head than in those from the intertrochanteric region. Conclusion. Idiopathic ONFH is associated with a reduced mineralization capacity of osteoblasts and increased secretion of pro-resorptive factors. Cite this article: Bone Joint Res 2021;10(9):619–628

Aims. Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model. Methods. Guinea pigs aged between six and seven months of age were randomized into control or treatment groups. Three- or four-month-old guinea pigs served as the young control group. The knees were administered 40 μl intra-articular injections of 10 nM PTH or vehicle once a week for three months. Their endurance as determined from time on the treadmill was evaluated before kill. Their tibial plateaus were analyzed using microcalculated tomography (μCT) and histological studies. Results. PTH increased the endurance on the treadmill test, preserved glycosaminoglycans, and reduced Osteoarthritis Research Society International score and chondrocyte apoptosis rate. No difference was observed in the subchondral plate bone density or metaphyseal trabecular bone volume and bone morphogenetic 2 protein staining. Conclusion. Subchondral bone is crucial in the initiation and progression of OA. Although previous studies have shown that subcutaneous PTH alleviates knee OA by improving subchondral and metaphyseal bone mass, we demonstrated that intra-articular PTH injections improved spontaneous OA by directly affecting the cartilage rather than the subchondral or metaphyseal bone in a preclinical age-related OA model. Cite this article: Bone Joint Res 2021;10(8):514–525

Aims. To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMDSV) for alleviation of the progression of osteoarthritis (OA) in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ). Methods. In vitro, OA chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV), and UTMDSV on alternate days for four weeks. Chondrocytes were also treated with PPARγ inhibitor, PPARγ inhibitor+ UTMDSV, and UTMDSV. The cholesterol efflux rate and triglyceride levels were measured using an assay kit and oil red O staining, respectively. In vivo, the OA rabbits were treated with a single intra-articular injection of UTMD, SV, and UTMDSV every seven days for four weeks. Cartilage histopathology was assessed by safranin-O staining and the Mankin score. Total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) in rabbit knee synovial fluid were detected by enzyme-marker assay. Aggrecan, collagen II, and PPARγ expression levels were analyzed by Western blotting (WB). Results. In vitro, UTMDSV significantly increased the cholesterol efflux rate and aggrecan, collagen II, and PPARγ levels in OA chondrocytes; these effects were blocked by the PPARγ inhibitor. In vivo, UTMD. SV. significantly increased aggrecan, collagen II, PPARγ, and HDL-C levels, while TC levels and Mankin scores were decreased compared with the UTMD, SV, OA, and control groups. Conclusion. UTMDSV promotes cartilage extracellular matrix synthesis by modulating the PPARγ-mediated cholesterol efflux pathway in OA rabbits. Cite this article: Bone Joint Res 2021;10(10):693–703

Aims. Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model. Methods. The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA). Results. PARP-1 expression level significantly increased in the cartilage of the established OA rat model. sh-PARP-1 treatment suppressed PARP-1 levels, decreased the Δ Force (the difference between the weight on ipsilateral limb and contralateral limb) and the knee joint width, inhibited cartilage matrix catabolic enzymes, and ameliorated OA cartilage degradation and attenuated inflammatory response. Conclusion. PARP-1 inhibition attenuates OA cartilage inflammatory response in the OA rat model. Cite this article: Bone Joint Res 2021;10(7):401–410

Aims. This study aimed to investigate the incidence of ≥ 5 mm asymmetry in lower and whole leg lengths (LLs) in patients with unilateral osteoarthritis (OA) secondary to developmental dysplasia of the hip (DDH-OA) and primary hip osteoarthritis (PHOA), and the relationship between lower and whole LL asymmetries and femoral length asymmetry. Methods. In total, 116 patients who underwent unilateral total hip arthroplasty were included in this study. Of these, 93 had DDH-OA and 23 had PHOA. Patients with DDH-OA were categorized into three groups: Crowe grade I, II/III, and IV. Anatomical femoral length, femoral length greater trochanter (GT), femoral length lesser trochanter (LT), tibial length, foot height, lower LL, and whole LL were evaluated using preoperative CT data of the whole leg in the supine position. Asymmetry was evaluated in the Crowe I, II/III, IV, and PHOA groups. Results. The incidences of whole and lower LL asymmetries were 40%, 62.5%, 66.7%, and 26.1%, and 21.7%, 20.8%, 55.6%, and 8.7% in the Crowe I, II/III, and IV, and PHOA groups, respectively. The incidence of tibial length asymmetry was significantly higher in the Crowe IV group (44.4%) than that in the PHOA group (4.4%). In all, 50% of patients with DDH-OA with femoral length GT and LT asymmetries had lower LL asymmetry, and 75% had whole LL asymmetry. The incidences of lower and whole LL asymmetries were 20% and 42.9%, respectively, even in the absence of femoral length GT and LT asymmetries. Conclusion. Overall, 43% of patients with unilateral DDH-OA without femoral length asymmetry had whole LL asymmetry of ≥ 5 mm. Thus, both the femur length and whole LL should be measured to accurately assess LL discrepancy in patients with unilateral DDH-OA. Cite this article: Bone Jt Open 2024;5(2):79–86

Aims. As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA). Methods. Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections. Results. Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. Conclusion. This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies. Cite this article: Bone Joint Res 2023;12(1):58–71

Aims. The prevalence of osteoarthritis (OA) associated with instability of the shoulder ranges between 4% and 60%. Articular cartilage is, however, routinely assessed in these patients using radiographs or scans (2D or 3D), with little opportunity to record early signs of cartilage damage. The aim of this study was to assess the prevalence and localization of chondral lesions and synovial damage in patients undergoing arthroscopic surgery for instablility of the shoulder, in order to classify them and to identify risk factors for the development of glenohumeral OA. Methods. A total of 140 shoulders in 140 patients with a mean age of 28.5 years (15 to 55), who underwent arthroscopic treatment for recurrent glenohumeral instability, were included. The prevalence and distribution of chondral lesions and synovial damage were analyzed and graded into stages according to the division of the humeral head and glenoid into quadrants. The following factors that might affect the prevalence and severity of chondral damage were recorded: sex, dominance, age, age at the time of the first dislocation, number of dislocations, time between the first dislocation and surgery, preoperative sporting activity, Beighton score, type of instability, and joint laxity. Results. A total of 133 patients (95%) had synovial or chondral lesions. At the time of surgery, shoulders were graded as having mild, moderate, and severe OA in 55 (39.2%), 72 (51.4%), and six (4.2%) patients, respectively. A Hill-Sachs lesion and fibrillation affecting the anteroinferior glenoid cartilage were the most common findings. There was a significant positive correlation between the the severity of the development of glenohumeral OA and the patient’s age, their age at the time of the first dislocation, and the number of dislocations (p = 0.004, p = 0.011, and p = 0.031, respectively). Conclusion. Synovial inflammation and chondral damage associated with instability of the shoulder are more prevalent than previously reported. The classification using quadrants gives surgeons more information about the chondral damage, and could explain the pattern of development of glenohumeral OA after stabilization of the shoulder. As the number of dislocations showed a positive correlation with the development of OA, this might be an argument for early stabilization. Cite this article: Bone Joint J 2024;106-B(10):1125–1132

Aims. Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants. Methods. pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 10. 9. particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs. Results. Significantly higher content of DNA and collagen was observed for the pEV-treated group compared to control and cEV groups. No differences were found in GAG quantification nor in EVs uptake within any treated group. Conclusion. In conclusion, pEVs showed better performance than cEVs in our in vitro OA model. Although further studies are needed, pEVs are shown as a potential alternative to cEVs for cell-free regenerative medicine. Cite this article: Bone Joint Res 2023;12(10):667–676

Aims. Pelvic tilt is believed to affect the symptomology of osteoarthritis (OA) of the hip by alterations in joint movement, dysplasia of the hip by modification of acetabular cover, and femoroacetabular impingement by influencing the impingement-free range of motion. While the apparent role of pelvic tilt in hip pathology has been reported, the exact effects of many forms of treatment on pelvic tilt are unknown. The primary aim of this study was to investigate the effects of surgery on pelvic tilt in these three groups of patients. Methods. The demographic, radiological, and outcome data for all patients operated on by the senior author between October 2016 and January 2020 were identified from a prospective registry, and all those who underwent surgery with a primary diagnosis of OA, dysplasia, or femoroacetabular impingement were considered for inclusion. Pelvic tilt was assessed on anteroposterior (AP) standing radiographs using the pre- and postoperative pubic symphysis to sacroiliac joint (PS-SI) distance, and the outcomes were assessed with the Hip Outcome Score (HOS), International Hip Outcome Tool (iHOT-12), and Harris Hip Score (HHS). Results. The linear regression model revealed a significant negative predictive association between the standing pre- and postoperative PS-SI distances for all three groups of patients (all p < 0.001). There was a significant improvement in all three outcome measures between the pre- and postoperative values (p < 0.05). Conclusion. There is a statistically significant decrease in pelvic tilt after surgery in patients with OA of the hip, dysplasia, and femoroacetabular impingement. These results confirm that surgery significantly alters the pelvic orientation. Pelvic tilt significantly decreased after total hip arthroplasty, periacetabular osteotomy, and arthroscopy/surgical hip dislocation. The impact of surgery on pelvic tilt should be considered within the therapeutic plan in order to optimize pelvic orientation in these patients. Cite this article: Bone Joint J 2022;104-B(9):1025–1031

Aims. The objective of this study was to present the outcomes of rotational acetabular osteotomy (RAO) over a 30-year period for osteoarthritis (OA) secondary to dysplasia of the hip in pre- or early-stage OA. Methods. Between September 1987 and December 1994, we provided treatment to 47 patients (55 hips) with RAO for the management of pre- or early-stage OA due to developmental hip dysplasia. Of those, eight patients (11 hips) with pre-OA (follow-up rate 79%) and 27 patients (32 hips) with early-stage OA (follow-up rate 78%), totalling 35 patients (43 hips) (follow-up rate 78%), were available at a minimum of 28 years after surgery. Results. In the pre-OA group, the mean Merle d'Aubigné score improved significantly from 14.5 points (SD 0.7) preoperatively to 17.4 points at final follow-up (SD 1.2; p = 0.004) and in the early-stage group, the mean score did not improve significantly from 14.0 (SD 0.3) to 14.6 (SD 2.4; p = 0.280). Radiologically, the centre-edge angle, acetabular roof angle, and head lateralization index were significantly improved postoperatively in both groups. Radiological progression of OA was observed in two patients (two hips) in the pre-OA group and 17 patients (18 hips) in the early-stage group. Kaplan-Meier survival analysis, with radiological progression of OA as the primary outcome, projected a 30-year survival rate of 81.8% (95% confidence interval (CI) 0.59 to 1.00) for the pre-OA group and 42.2% (95% CI 0.244 to 0.600) for the early-stage group. In all cases, the overall survival rate stood at 51.5% (95% CI 0.365 to 0.674) over a 30-year period, and when the endpoint was conversion to total hip arthroplasty, the survival rate was 74.0% (95% CI 0.608 to 0.873). Conclusion. For younger patients with pre-OA, joint preservation of over 30 years can be expected after RAO. Cite this article: Bone Joint J 2024;106-B(5 Supple B):25–31

Aims. The Coronal Plane Alignment of the Knee (CPAK) classification has been developed to predict individual variations in inherent knee alignment. The impact of preoperative and postoperative CPAK classification phenotype on the postoperative clinical outcomes of total knee arthroplasty (TKA) remains elusive. This study aimed to examine the effect of postoperative CPAK classification phenotypes (I to IX), and their pre- to postoperative changes on patient-reported outcome measures (PROMs). Methods. A questionnaire was administered to 340 patients (422 knees) who underwent primary TKA for osteoarthritis (OA) between September 2013 and June 2019. A total of 231 patients (284 knees) responded. The ­Knee Society Score 2011 (KSS 2011), Knee injury and Osteoarthritis Outcome Score-12 (KOOS-12), and Forgotten Joint Score-12 (FJS-12) were used to assess clinical outcomes. Using preoperative and postoperative anteroposterior full-leg radiographs, the arithmetic hip-knee-ankle angle (aHKA) and joint line obliquity (JLO) were calculated and classified based on the CPAK classification. To investigate the impact on PROMs, multivariable regression analyses using stepwise selection were conducted, considering factors such as age at surgery, time since surgery, BMI, sex, implant use, postoperative aHKA classification, JLO classification, and changes in aHKA and JLO classifications from preoperative to postoperative. Results. The preoperative and postoperative CPAK classifications were predominantly phenotype I (155 knees; 55%) and phenotype V (73 knees; 26%), respectively. The change in the preoperative to postoperative aHKA classification was a significant negative predictive factor for KOOS-12 and FJS-12, while postoperative apex proximal JLO was a significant negative predictive factor for KSS 2011 and KOOS-12. Conclusion. In primary TKA for OA, preoperative and postoperative CPAK phenotypes were associated with PROMs. Alteration in varus/valgus alignment from preoperative to postoperative was recognized as a negative predictive factor for both KOOS-12 and FJS-12. Moreover, the postoperative apex proximal JLO was identified as a negative factor for KSS 2011 and KOOS-12. Determining the target alignment for each preoperative phenotype with reproducibility could improve PROMs. Cite this article: Bone Joint J 2024;106-B(10):1059–1066

Aims. The aim of this study was to estimate the 90-day periprosthetic joint infection (PJI) rates following total knee arthroplasty (TKA) and total hip arthroplasty (THA) for osteoarthritis (OA). Methods. This was a data linkage study using the New South Wales (NSW) Admitted Patient Data Collection (APDC) and the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), which collect data from all public and private hospitals in NSW, Australia. Patients who underwent a TKA or THA for OA between 1 January 2002 and 31 December 2017 were included. The main outcome measures were 90-day incidence rates of hospital readmission for: revision arthroplasty for PJI as recorded in the AOANJRR; conservative definition of PJI, defined by T84.5, the PJI diagnosis code in the APDC; and extended definition of PJI, defined by the presence of either T84.5, or combinations of diagnosis and procedure code groups derived from recursive binary partitioning in the APDC. Results. The mean 90-day revision rate for infection was 0.1% (0.1% to 0.2%) for TKA and 0.3% (0.1% to 0.5%) for THA. The mean 90-day PJI rates defined by T84.5 were 1.3% (1.1% to 1.7%) for TKA and 1.1% (0.8% to 1.3%) for THA. The mean 90-day PJI rates using the extended definition were 1.9% (1.5% to 2.2%) and 1.5% (1.3% to 1.7%) following TKA and THA, respectively. Conclusion. When reporting the revision arthroplasty for infection, the AOANJRR substantially underestimates the rate of PJI at 90 days. Using combinations of infection codes and PJI-related surgical procedure codes in linked hospital administrative databases could be an alternative way to monitor PJI rates. Cite this article: Bone Joint J 2022;104-B(9):1060–1066

Aims. To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA). Methods. The data from 348 patients who had RA or osteoarthritis (OA) and had previously undergone a total knee (TKA) and/or a total hip arthroplasty (THA) (including RA-PJI: 60 cases, RA-non-PJI: 80 cases; OA-PJI: 104 cases, OA-non-PJI: 104 cases) were retrospectively analyzed. A receiver operating characteristic curve was used to determine the optimal thresholds of the CRP, ESR, synovial fluid white blood cell count (WBC), and polymorphonuclear neutrophil percentage (PMN%) for diagnosing RA-PJI and OA-PJI. The diagnostic efficacy was evaluated by comparing the area under the curve (AUC) of each index and applying the results of the combined index diagnostic test. Results. For PJI prediction, the results of serological and synovial fluid indexes were different between the RA-PJI and OA-PJI groups. The optimal cutoff value of CRP for diagnosing RA-PJI was 12.5 mg/l, ESR was 39 mm/hour, synovial fluid WBC was 3,654/μl, and PMN% was 65.9%; and those of OA-PJI were 8.2 mg/l, 31 mm/hour, 2,673/μl, and 62.0%, respectively. In the RA-PJI group, the specificity (94.4%), positive predictive value (97.1%), and AUC (0.916) of synovial fluid WBC were higher than those of the other indexes. The optimal cutoff values of synovial fluid WBC and PMN% for diagnosing RA-PJI after THA were significantly higher than those of TKA. The specificity and positive predictive value of the combined index were 100%. Conclusion. Serum inflammatory and synovial fluid indexes can be used for diagnosing RA-PJI, for which synovial fluid WBC is the best detection index. Combining multiple detection indexes can provide a reference basis for the early and accurate diagnosis of RA-PJI. Cite this article: Bone Joint Res 2023;12(9):559–570

Aims. Despite new technologies for total knee arthroplasty (TKA), approximately 20% of patients are dissatisfied. A major reason for dissatisfaction and revision surgery after TKA is persistent pain. The radiological grade of osteoarthritis (OA) preoperatively has been investigated as a predictor of the outcome after TKA, with conflicting results. The aim of this study was to determine if there is a difference in the intensity of pain 12 months after TKA in relation to the preoperative radiological grade of OA alone, and the combination of the intensity of preoperative pain and radiological grade of OA. Methods. The preoperative data of 300 patients who underwent primary TKA were collected, including clinical information (age, sex, preoperative pain), psychological variables (depression, anxiety, pain catastrophizing, anticipated pain), and quantitative sensory testing (temporal summation, pressure pain thresholds, conditioned pain modulation). The preoperative radiological severity of OA was graded according to the Kellgren-Lawrence (KL) classification. Persistent pain in the knee was recorded 12 months postoperatively. Generalized linear models explored differences in postoperative pain according to the KL grade, and combined preoperative pain and KL grade. Relative risk models explored which preoperative variables were associated with the high preoperative pain/low KL grade group. Results. Pain 12 months after TKA was not associated with the preoperative KL grade alone. Significantly increased pain 12 months after TKA was found in patients with a combination of high preoperative pain and a low KL grade (p = 0.012). Patients in this group were significantly more likely to be male, younger, and have higher preoperative pain catastrophizing, higher depression, and lower anxiety (all p ≤ 0.05). Conclusion. Combined high preoperative pain and low radiological grade of OA, but not the radiological grade alone, was associated with a higher intensity of pain 12 months after primary TKA. This group may have a more complex cause of pain that requires additional psychological interventions in order to optimize the outcome of TKA. Cite this article: Bone Joint J 2022;104-B(11):1202–1208

Aims. This study aimed to investigate whether human umbilical cord mesenchymal stem cells (UC-MSCs) can prevent articular cartilage degradation and explore the underlying mechanisms in a rat osteoarthritis (OA) model induced by monosodium iodoacetate (MIA). Methods. Human UC-MSCs were characterized by their phenotype and multilineage differentiation potential. Two weeks after MIA induction in rats, human UC-MSCs were intra-articularly injected once a week for three weeks. The therapeutic effect of human UC-MSCs was evaluated by haematoxylin and eosin, toluidine blue, Safranin-O/Fast green staining, and Mankin scores. Markers of joint cartilage injury and pro- and anti-inflammatory markers were detected by immunohistochemistry. Results. Histopathological analysis showed that intra-articular injection of human UC-MSCs significantly inhibited the progression of OA, as demonstrated by reduced cartilage degradation, increased Safranin-O staining, and lower Mankin scores. Immunohistochemistry showed that human UC-MSC treatment down-regulated the expression of matrix metalloproteinase-13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), and enhanced the expression of type II collagen and ki67 in the articular cartilage. Furthermore, human UC-MSCs significantly decreased the expression of interleukin (IL)-1β and tumour necrosis factor-α (TNF-α), while increasing TNF-α-induced protein 6 and IL-1 receptor antagonist. Conclusion. Our results demonstrated that human UC-MSCs ameliorate MIA-induced OA by preventing cartilage degradation, restoring the proliferation of chondrocytes, and inhibiting the inflammatory response, which implies that human UC-MSCs may be a promising strategy for the treatment of OA. Cite this article: Bone Joint Res 2021;10(3):226–236

Aims. To assess the incidence of radiological lateral osteoarthritis (OA) at 15 years after medial unicompartmental knee arthroplasty (UKA) and assess the relationship of lateral OA with symptoms and patient characteristics. Methods. Cemented Phase 3 medial Oxford UKA implanted by two surgeons since 1998 for the recommended indications were prospectively followed. A 15-year cumulative revision rate for lateral OA of 5% for this series was previously reported. A total of 163 unrevised knees with 15-year (SD 1) anterior-posterior knee radiographs were studied. Lateral joint space width (JSW. L. ) was measured and severity of lateral OA was classified as: nil/mild, moderate, and severe. Preoperative and 15-year Oxford Knee Scores (OKS) and American Knee Society Scores were determined. The effect of age, sex, BMI, and intraoperative findings was analyzed. Statistical analysis included one-way analysis of variance and Kruskal-Wallis H test, with significance set at 5%. Results. The mean age was 80.6 years (SD 8.3), with 84 females and 79 males. The mean JSW. L. was 5.6 mm (SD 1.4), and was not significantly related to age, sex, or intraoperative findings. Those with BMI > 40 kg/m. 2. had a smaller JSW. L. than those with a ‘normal’ BMI (p = 0.039). The incidence of severe and moderate lateral OA were both 4.9%. Overall, 2/142 (1.4%) of those with nil/mild lateral OA, 1/8 (13%) with moderate, and 2/8 (25%) with severe subsequently had a revision. Those with severe (mean OKS 35.6 (SD 9.3)) and moderate OA (mean OKS 35.8 (SD 10.5)) tended to have worse outcome scores than those with nil/mild (mean OKS 39.5 (SD 9.2)) but the difference was only significant for OKS-Function (p = 0.044). Conclusion. This study showed that the rate of having severe or moderate radiological lateral OA at 15 years after medial UKA was low (both 4.9%). Although patients with severe or moderate lateral OA had a lower OKS than those with nil/mild OA, their mean scores (OKS 36) would be classified as good. Cite this article: Bone Jt Open 2023;4(3):210–218

Aims. Despite higher rates of revision after total hip arthroplasty (THA) being reported for uncemented stems in patients aged > 75 years, they are frequently used in this age group. Increased mortality after cemented fixation is often used as a justification, but recent data do not confirm this association. The aim of this study was to investigate the influence of the design of the stem and the type of fixation on the rate of revision and immediate postoperative mortality, focusing on the age and sex of the patients. Methods. A total of 333,144 patients with primary osteoarthritis (OA) of the hip who underwent elective THA between November 2012 and September 2022, using uncemented acetabular components without reconstruction shells, from the German arthroplasty registry were included in the study. The revision rates three years postoperatively for four types of stem (uncemented, uncemented with collar, uncemented short, and cemented) were compared within four age groups: < 60 years (Young), between 61 and 70 years (Mid-I), between 71 and 80 years (Mid-II), and aged > 80 years (Old). A noninferiority analysis was performed on the most frequently used designs of stem. Results. The design of the stem was found to have no significant influence on the rate of revision for either sex in the Young group. Uncemented collared stems had a significantly lower rate of revision compared with the other types of stem for females in the Mid-I group. There was a significantly higher rate of revision for uncemented stems in females in the Mid-II group compared with all other types of stem, while in males the rate for uncemented stems was only significantly higher than the rate for cemented stems. Cemented stems had a significantly lower revision rate compared with uncemented and short stems for both sexes in the Old cohort, as did females with collared stems. The rate of immediate postoperative mortality was similar for all types of stem in the Old age group, as were the American Society of Anesthesiologists grades. Conclusion. In patients aged > 80 years, uncemented and short stems had significantly higher revision rates compared with cemented and collared stems, especially in females. The design of the stem and type of fixation have to be analyzed in more detail than only considering cemented and uncemented fixation, in order to further improve the success of THA. Cite this article: Bone Joint J 2024;106-B(3 Supple A):130–136

Aims. Metal and ceramic humeral head bearing surfaces are available choices in anatomical shoulder arthroplasties. Wear studies have shown superior performance of ceramic heads, however comparison of clinical outcomes according to bearing surface in total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) is limited. This study aimed to compare the rates of revision and reoperation following metal and ceramic humeral head TSA and HA using data from the National Joint Registry (NJR), which collects data from England, Wales, Northern Ireland, Isle of Man and the States of Guernsey. Methods. NJR shoulder arthroplasty records were linked to Hospital Episode Statistics and the National Mortality Register. TSA and HA performed for osteoarthritis (OA) in patients with an intact rotator cuff were included. Metal and ceramic humeral head prostheses were matched within separate TSA and HA groups using propensity scores based on 12 and 11 characteristics, respectively. The primary outcome was time to first revision and the secondary outcome was non-revision reoperation. Results. A total of 4,799 TSAs (3,578 metal, 1,221 ceramic) and 1,363 HAs (1,020 metal, 343 ceramic) were included. The rate of revision was higher for metal compared with ceramic TSA, hazard ratio (HR) 3.31 (95% confidence interval (CI) 1.67 to 6.58). At eight years, prosthesis survival for ceramic TSA was 98.7% (95% CI 97.3 to 99.4) compared with 96.4% (95% CI 95.2 to 97.3) for metal TSA. The majority of revision TSAs were for cuff insufficiency or instability/dislocation. There was no significant difference in the revision rate for ceramic compared with metal head HA (HR 1.33 (95% CI 0.76 to 2.34)). For ceramic HA, eight-year prosthetic survival was 92.8% (95% CI 86.9 to 96.1), compared with 91.6% (95% CI 89.3 to 93.5) for metal HA. The majority of revision HAs were for cuff failure. Conclusion. The rate of all-cause revision was higher following metal compared with ceramic humeral head TSA in patients with OA and an intact rotator cuff. There was no difference in the revision rate for HA according to bearing surface. Cite this article: Bone Joint J 2024;106-B(5):482–491

Aims. Hereditary haemochromatosis is a genetic disorder that is caused by several known mutations in the human homeostatic iron regulator protein (HFE) gene. Abnormal accumulation of iron causes a joint disease that resembles osteoarthritis (OA), but appears at a relatively younger age and is accompanied by cirrhosis, diabetes, and injury to other organs. Increased serum transferrin saturation and ferritin levels are known markers of haemochromatosis with high positive predictive values. Methods. We have retrospectively analyzed the iron studies of a cohort of 2,035 patients undergoing knee joint arthroplasty due to OA. Results. No patients had HFE gene C282Y, S65C, or H63D mutations testing. In total, 18 patients (2.96%) of the male cohort and 51 (3.58%) of the female cohort had pathologically increased ferritin levels that may be indicative of haemochromatosis. Seven patients (0.34%) had serum transferrin saturation above 45%. Conclusion. The awareness for the diagnosis of this disorder in Orthopaedics is low and needs improvement. Osteoarthritic patients undergoing knee arthroplasty should be routinely screened for haemochromatosis by iron studies and referred to genetic testing when needed. Level of evidence: Level III - Retrospective cohort study. Cite this article: Bone Jt Open 2021;2(12):1062–1066

Aims. The gluteus minimus (GMin) and gluteus medius (GMed) have unique structural and functional segments that may be affected to varying degrees, by end-stage osteoarthritis (OA) and normal ageing. We used data from patients with end-stage OA and matched healthy controls to 1) quantify the atrophy of the GMin and GMed in the two groups and 2) describe the distinct patterns of the fatty infiltration in the different segments of the GMin and GMed in the two groups. Methods. A total of 39 patients with end-stage OA and 12 age- and sex frequency-matched healthy controls were prospectively enrolled in the study. Fatty infiltration within the different segments of the GMin and the GMed was assessed on MRI according to the semiquantitative classification system of Goutallier and normalized cross-sectional areas were measured. Results. The GMin was smaller in the OA-group (p < 0.001) compared to the control group, but there was no group difference in the size of the GMed (p = 0.101). Higher levels of fatty infiltration were identified in the anterior segment of the GMin (p = 0.006) and the anterior (p = 0.006) and middle (p = 0.047) segments of the GMed in the OA group. All subjects in the control group had fatty infiltration of the anterior segment of the GMin, but all except one had no fatty infiltration in the entire GMed. Conclusion. End-stage OA was associated with significant atrophy of the GMin and higher levels of fatty infiltration, particularly in the anterior segments of the GMin and GMed. Minor fatty infiltration of the anterior segment of GMin appears to be a normal part of ageing. Our study has demonstrated different patterns of atrophy and fatty infiltration between patients with end-stage OA and healthy matched peers. Cite this article: Bone Jt Open 2021;2(1):40–47