Bone age is a radiographical assessment used in pediatric medicine due to its relative objectivity in determining biological maturity compared to chronological age and size.1 Currently, Greulich and Pyle (GP) is one of the most common methods used to determine bone age from hand radiographs.2–4 In recent years, new methods were developed to increase the efficiency in bone age analysis like the shorthand bone age (SBA) and the automated artificial intelligence algorithms. The purpose of this study is to evaluate the accuracy and reliability of these two methods and examine if the reduction in analysis time compromises their accuracy. Two hundred thirteen males and 213 females were selected. Each participant had their bone age determined by two separate raters using the GP (M1) and SBA methods (M2). Three weeks later, the two raters repeated the analysis of the radiographs. The raters timed themselves using an online stopwatch while analyzing the radiograph on a computer screen. De-identified radiographs were securely uploaded to an automated algorithm developed by a group of radiologists in Toronto. The gold standard was determined to be the radiology report attached to each radiograph, written by experienced radiologists using GP (M1). For intra-rater variability, intraclass correlation analysis between trial 1 (T1) and trial 2 (T2) for each rater and method was performed. For inter-rater variability, intraclass correlation was performed between rater 1 (R1) and rater 2 (R2) for each method and trial. Intraclass correlation between each method and the gold standard fell within the 0.8–0.9 range, highlighting significant agreement. Most of the comparisons showed a statistically significant difference between the two new methods and the gold standard; however it may not be clinically significant as it ranges between 0.25–0.5 years. A bone age is considered clinically abnormal if it falls outside 2 standard deviations of the chronological age; standard deviations are calculated and provided in GP atlas.6–8 For a 10-year old female, 2 standard deviations constitute 21.6 months which far outweighs the difference reported here between SBA, automated algorithm and the gold standard. The median time for completion using the GP method was 21.83 seconds for rater 1 and 9.30 seconds for rater 2. In comparison, SBA required a median time of 7 seconds for rater 1 and 5 seconds for rater 2. The automated method had no time restraint as bone age was determined immediately upon radiograph upload. The correlation between the two trials in each method and rater (i.e. R1M1T1 vs R1M1T2) was excellent (κ= 0.9–1) confirming the reliability of the two new methods. Similarly, the correlation between the two raters in each method and trial (i.e. R1M1T1 vs R2M1T1) fell within the 0.9–1 range. This indicates a limited variability between raters who may use these two methods. The shorthand bone age method and an artificial intelligence automated algorithm produced values that are in agreement with the gold standard Greulich and Pyle, while reducing analysis time and maintaining a high inter-rater and intra-rater reliability

Purpose of the study: Determining bone age at the wrist is not an easy task and can be a source of error. We elaborated a method for determining bone age at the elbow using an analysis of bone maturation at this localization. Material and methods: The method finetunes the Sauvegrain method and is based on more than ten years of data for the analysis of more than 3600 x-rays. Bone maturation evolves from 0% at birth to 100% marking the end of growth. We propose a digital system for drawing the growth curve from 50% to 100% bone maturation as a function of chronological age. This curve gives the distribution of bone age around the median for each gender. Fifty percent maturation corresponds to onset of adolescence and can be used to define onset of puberty before any other clinical sign; 100% bone maturation corresponds to maximal growth or stature. Specific bone landmarks are used and the method for calculating bone age is presented. Results: It is interesting that a shift of one year or more between bone age calculated at the elbow and that calculated from the wrist. This observation was frequent and suggests that bone age determined at the elbow gives a better reflection of limb maturation. In addition, regular use of this method in daily practice confirmed its usefulness, reliability, and inter- and intra-observer reproducibility. Conclusion: This is a reliable simple method for determining bone maturation. It is easier to use than the wrist method and probably better reflects bone maturation of the limbs

Introduction: Prophylactic pinning of an asymptomatic hip in SCFE is controversial. Bone age has been used as evidence of future contralateral slip risk and used as an indication for such intervention. The efficacy of bone age assessment at predicting contralateral slip was tested in this study. Patients and Methods: 18 Caucasian children prospectively had bone age assessment using wrist and hand x-rays when presenting with a unilateral SCFE. Patients and parents were informed about the chance of con-tralateral slip and risks of prophylactic fixation, and advised to attend hospital immediately on development of symptoms in contralateral hip. After in-situ fixation of the affected side prospective monitoring in outpatient department was performed. Surgical intervention was undertaken if the contralateral hip was symptomatic. Results: Three children (2 boys) went on to develop to a contralateral slip at a mean of 20 months from initial presentation. 6 children (5 boys) were deemed at risk of contralateral slip due to a bone age below 12.5 years for boys and 10.5 for girls. Only one from this group developed a contralateral slip. The relative risk of proceeding to contralateral slip when the bone age is below the designated values was 1 (95% confidence interval of 0.1118 to 8.95). The sensitivity and specificity were 33% and 66% respectively. With positive predictive value of 15% and diagnostic efficiency of 61%. Conclusion: Delayed bone age by itself is not a good predictor of future contralateral slip at initial presentation. Routine prophylactic pinning is not justified based on bone age alone, with the risks of surgical fixation it carries. Prospective long term longitudinal study is required

Introduction: Prophylactic pinning of an asymptomatic hip in SCFE is controversial. Bone age has been used as evidence of future contralateral slip risk and used as an indication for such intervention. The efficacy of bone age assessment at predicting contralateral slip was tested in this study. Patients and Methods: 18 Caucasian children prospectively had bone age assessment using wrist and hand x-rays when presenting with a unilateral SCFE. Patients and parents were informed about the chance of contralateral slip and risks of prophylactic fixation, and advised to attend hospital immediately on development of symptoms in contralateral hip. After in-situ fixation of the affected side prospective monitoring in outpatient department was performed. Surgical intervention was undertaken if the contralateral hip was symptomatic. Results: Three children (2 boys) went on to develop to a contralateral slip at a mean of 20 months from initial presentation. 6 children (5 boys) were deemed at risk of contralateral slip due to a bone age below 12.5 years for boys and 10.5 for girls. Only one from this group developed a contralateral slip. The relative risk of proceeding to contralateral slip when the bone age is below the designated values was 1 (95% confidence interval of 0.1118 to 8.95). Conclusion: Delayed bone age by itself is not a good predictor of future contralateral slip at initial presentation. Routine prophylactic pinning is not justified based on bone age alone, with the risks of surgical fixation it carries. Prospective long term longitudinal study is required

Introduction: Prophylactic pinning of an asymptomatic hip in SCFE is controversial. Bone age has been used as evidence of future contralateral slip risk and used as an indication for such intervention. The efficacy of bone age assessment at predicting contralateral slip was tested in this study. Patients and Methods: 18 Caucasian children prospectively had bone age assessment using wrist and hand x-rays when presenting with a unilateral SCFE. Patients and parents were informed about the chance of con-tralateral slip and risks of prophylactic fixation, and advised to attend hospital immediately on development of symptoms in contralateral hip. After in-situ fixation of the affected side prospective monitoring in outpatient department was performed. Surgical intervention was undertaken if the contralateral hip was symptomatic. Results: Three children (2 boys) went on to develop to a contralateral slip at a mean of 20 months from initial presentation. 6 children (5 boys) were deemed at risk of contralateral slip due to a bone age below 12.5 years for boys and 10.5 for girls. Only one from this group developed a contralateral slip. The relative risk of proceeding to contralateral slip when the bone age is below the designated values was 1 (95% confidence interval of 0.1118 to 8.95). The sensitivity and specificity were 33% and 66% respectively. With positive predictive value of 15% and diagnostic efficiency of 61%. Conclusion: Delayed bone age by itself is not a good predictor of future contralateral slip at initial presentation. Routine prophylactic pinning is not justified based on bone age alone, with the risks of surgical fixation it carries. Prospective long term longitudinal study is required

A chance observation of asymmetrical bone ages in a child with spastic hemiplegia stimulated a prospective gathering of bilateral hand radiographs in 33 hemiplegic patients, and on a single occasion in a control group of 23 patients with leg length discrepancy in the absence of neurological disorder. The bone age assessments according to Greulich and Pyle, which by convention has used the left hand only, were done by a single expert observer blinded to the clinical details. 13 hemiplegic patients (39%) had delayed bone ages of 6 months or more. When present it was always delayed on the hemiplegic side. The mean delay for the whole group was 2.5 months, whereas there was no mean difference in the control group (p = 0.001). The oldest bone age with asymmetry was 14.5 years in males and 12 years in females, indicating that when present the delay “catches up” in the last 2-3 years of growth. In hemiplegia the percentage leg length discrepancy also tends to decrease during later growth, and after 80% of growth the hemiplegic side outgrows the normal leg by a mean of 0.3cm/year. No correlation could be found between the delay of bone age and the severity of either the neurological abnormality or the actual discrepancy of length. The implications for clinical management will be discussed

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA. Cite this article: Bone Joint Res 2023;12(9):536–545

Objectives: Nowadays estimating paediatric bone age is done using methods based on standards from the 50’s and 70’s. These methods are often difficult to perform, they require experience in the analysis of multiple bones and are based on subjective measures. Many times, the age calculated stands within a wide range of age interval. We investigate a new method based on AP foot X-rays. Material and Methods: 971 radiographs taken from 220 paediatric patients (0–18 years old) were analyzed. 34 different ratios were designed by measuring ossification centres of the bones of the first and second foot rays. These ratios were statistically studied searching for the relation with variables as gender, laterality, foot pathology and forefoot formulae. Finally, regression lines and curves from each ratio were calculated as well as their correlation with chronological age. Results: The best suited correlations are obtained with the ratios calculated from the epiphysis of the proximal phalange of the first and second toes. With them, multiple regression analysis is able to establish an equation that estimates bone age, with a chronological age correlation of 0,86 for general population, 0,85 for boys and 0,90 for girls (p< 0,01). It is applicable for either feet, and valid for every forefoot formula or pathologic feet. Conclusions: This new method is designed to estimate bone age in children using either plain radiographs or digital images. The method is objective, precise, universal and easy to calculate. It proves a good correlation in children between 1 and 13 years old. It is based on a modern population and adjusted with lineal regression equations to both genders

We assessed the Japanese specific bone age standard with Tanner-Whitehouse 2 (TW2) method for the evaluation of skeletal maturity in adolescent scoliosis. TW2 bone age was investigated by the left hand-wrist X-rays of 120 girls with adolescent scoliosis. Their chronological age ranged from 10.2 to 19.0 years. Because Risser’s sign is uncertain between Risser IV and V, for comparison of TW2 bone age with Risser’s sign, we classified apophyses that with an apparent narrowing of cartilage and that with a partial fusion as the later of Risser IV. In addition, clinical courses of the skeletal matured cases (adult bones) in 6 months before investigation were reviewed retrospectively. Even or less than 5 degrees change of Cobb’s angle was evaluated as unchanged. Furthermore, bone age distribution of immature cases was also reviewed for comparision of the unchanged group with the progressive group. None was evaluated as adult bone in the stage from Risser 0 to III. The rate of adult bone which was shown in Risser IV was 43.5%, but 88.9% was in the later of IV. 95.8% of Risser V was already adult bone. Moreover, 93.1% of adult bone was unchanged in their clinical courses. Remaining 4 cases (6.9%) was progressive, but had not progressed in the following 6 months. Bone ages of the progressive immature group distributed in the range from 11.7 to 13.9 years. Those of the unchanged immature group distributed mainly over 13.1 years. Although it is necessary to follow the immature longitudinally, adult bone appeared almost in the later of Risser IV, and appeared earlier than Risser V. And Cobb’s angle may become unchanged before adult bone. At least adult bone would be an indicator between Risser IV and V

Objectives. In total hip arthroplasty (THA), the cementless, tapered-wedge stem design contributes to achieving initial stability and providing optimal load transfer in the proximal femur. However, loading conditions on the femur following THA are also influenced by femoral structure. Therefore, we determined the effects of tapered-wedge stems on the load distribution of the femur using subject-specific finite element models of femurs with various canal shapes. Patients and Methods. We studied 20 femurs, including seven champagne flute-type femurs, five stovepipe-type femurs, and eight intermediate-type femurs, in patients who had undergone cementless THA using the Accolade TMZF stem at our institution. Subject–specific finite element (FE) models of pre- and post-operative femurs with stems were constructed and used to perform FE analyses (FEAs) to simulate single-leg stance. FEA predictions were compared with changes in bone mineral density (BMD) measured for each patient during the first post-operative year. Results. Stovepipe models implanted with large-size stems had significantly lower equivalent stress on the proximal-medial area of the femur compared with champagne-flute and intermediate models, with a significant loss of BMD in the corresponding area at one year post-operatively. Conclusions. The stovepipe femurs required a large-size stem to obtain an optimal fit of the stem. The FEA result and post-operative BMD change of the femur suggest that the combination of a large-size Accolade TMZF stem and stovepipe femur may be associated with proximal stress shielding. Cite this article: M. Oba, Y. Inaba, N. Kobayashi, H. Ike, T. Tezuka, T. Saito. Effect of femoral canal shape on mechanical stress distribution and adaptive bone remodelling around a cementless tapered-wedge stem. Bone Joint Res 2016;5:362–369. DOI: 10.1302/2046-3758.59.2000525

Introduction: The assessment of bone age using the standard Gruel and Pyle chart based on hand and wrist radiographs is usually carried out by Senior Radiologists. We performed a study to look at both intra and inter observer variability with different grades of clinicians. Materials and Methods: 30 sets of wrist radiographs were selected at random. The investigators included a Senior Radiographer, a Consultant and Registrar Radiologist an Orthopaedic Consultant and Senior Orthopaedic Fellow. Discussion: The Radiology team appear to be more consistent in their readings for the assessment of skeletal bone age than the Orthopaedic team. Howevr, it is interesting to note that although the Orthopaedic team are less consistent, when looking at the inter-observer variability, it suggests that both teams are equally well equipped to perform the task. Conclusion: Our study suggests that we should not cross professional boundaries. Render unto Caeser what is Ceaser’s!

Objectives. Bisphosphonates are widely used as first-line treatment for primary and secondary prevention of fragility fractures. Whilst they have proved effective in this role, there is growing concern over their long-term use, with much evidence linking bisphosphonate-related suppression of bone remodelling to an increased risk of atypical subtrochanteric fractures of the femur (AFFs). The objective of this article is to review this evidence, while presenting the current available strategies for the management of AFFs. Methods. We present an evaluation of current literature relating to the pathogenesis and treatment of AFFs in the context of bisphosphonate use. Results. Six broad themes relating to the pathogenesis and management of bisphosphonate-related AFFs are presented. The key themes in fracture pathogenesis are: bone microdamage accumulation; altered bone mineralisation and altered collagen formation. The key themes in fracture management are: medical therapy and surgical therapy. In addition, primary prevention strategies for AFFs are discussed. Conclusions. This article presents current knowledge about the relationship between bisphosphonates and the development of AFFs, and highlights key areas for future research. In particular, studies aimed at identifying at-risk subpopulations and organising surveillance for those on long-term therapy will be crucial in both increasing our understanding of the condition, and improving population outcomes. Cite this article: N. Kharwadkar, B. Mayne, J. E. Lawrence, V. Khanduja. Bisphosphonates and atypical subtrochanteric fractures of the femur. Bone Joint Res 2017;6:144–153. DOI: 10.1302/2046-3758.63.BJR-2016-0125.R1

Aims

The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI.

Metabolic bone diseases, such as osteoporosis and osteopetrosis, result from an imbalanced bone remodeling process. In vitro bone models are often used to investigate either bone formation or resorption independently, while in vivo, these processes are coupled. Combining these processes in a co-culture is challenging as it requires finding the right medium components to stimulate each cell type involved without interfering with the other cell type's differentiation. Furthermore, differentiation stimulating factors often comprise growth factors in supraphysiological concentrations, which can overshadow the cell-mediated crosstalk and coupling. To address these challenges, we aimed to recreate the physiological bone remodeling process, which follows a specific sequence of events starting with cell activation and bone resorption by osteoclasts, reversal, followed by bone formation by osteoblasts. We used a mineralized silk fibroin scaffold as a bone-mimetic template, inspired by bone's extracellular matrix composition and organization. Our model supported osteoclastic resorption and osteoblastic mineralization in the specific sequence that represents physiological bone remodeling. We also demonstrated how culture variables, such as different cell ratios, base media, and the use of osteogenic/osteoclast supplements, and the application of mechanical load, can be adjusted to represent either a high bone turnover system or a self-regulating system. The latter system did not require the addition of osteoclastic and osteogenic differentiation factors for remodeling, therefore avoiding growth factor use. Our in vitro model for bone remodeling has the potential to reduce animal experiments and advance in vitro drug development for bone remodeling pathologies like osteoporosis. By recreating the physiological bone remodeling cycle, we can investigate cell-cell and cell-matrix interactions, which are essential for understanding bone physiology and pathology. Furthermore, by tuning the culture variables, we can investigate bone remodeling under various conditions, potentially providing insights into the mechanisms underlying different bone disorders

Abstract. Objectives. Young patients receiving metallic bone implants after surgical resection of bone cancer require implants that last into adulthood, and ideally life-long. Porous implants with similar stiffness to bone can promote bone ingrowth and thus beneficial clinical outcomes. A mechanical remodelling stimulus, strain energy density (SED), is thought to be the primary control variable of the process of bone growth into porous implants. The sequential process of bone growth needs to be taken into account to develop an accurate and validated bone remodelling algorithm, which can be employed to improve porous implant design and achieve better clinical outcomes. Methods. A bone remodelling algorithm was developed, incorporating the concept of bone connectivity (sequential growth of bone from existing bone) to make the algorithm more physiologically relevant. The algorithm includes adaptive elastic modulus based on apparent bone density, using a node-based model to simulate local remodelling variations while alleviating numerical checkerboard problems. Strain energy density (SED) incorporating stress and strain effects in all directions was used as the primary stimulus for bone remodelling. The simulations were developed to run in MATLAB interfacing with the commercial FEA software ABAQUS and Python. The algorithm was applied to predict bone ingrowth into a porous implant for comparison against data from a sheep model. Results. The accuracy of the predicted bone remodelling was verified for standard loading cases (bending, torsion) against analytical calculations. Good convergence was achieved. The algorithm predicted good bone remodelling and growth into the investigated porous implant. Using the standard algorithm without connectivity, bone started to remodel at locations unconnected to any bone, which is physiologically implausible. The implementation of bone connectivity ensures the gradual process of bone growth into the implant pores from the sides. The bone connectivity algorithm predicted that the full remodelling required more time (approximately 50% longer), which should be considered when developing post-surgical rehabilitation strategies for patients. Both algorithms with and without bone connectivity implementation converged to same final stiffness (less than 0.01% difference). Almost all nodes reached the same density value, with only a limited number of nodes (less than 1%) in transition areas with a strong density gradient having noticeable differences. Conclusions. An improved bone remodelling algorithm based on strain energy density that modelled the sequential process of bone growth has been developed and tested. For a porous metallic bone implant the same final bone density distribution as for the original adaptive elasticity theory was predicted, with a slower and more fidelic process of growth from existing surrounding bone into the porous implant. 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

Introduction and Objective. Bone remodelling is a continuous process whereby osteocytes regulate the activity of osteoblasts and osteoclasts to repair loading-induced microdamage. While many in vitro studies have established the role of paracrine factors (e.g., RANKL/OPG) and cellular pathways involved in bone homeostasis, these techniques are generally limited to two-dimensional cell culture, which neglects the role of the native extracellular matrix in maintaining the phenotype of osteocyte. Recently, ex vivo models have been used to understand cell physiology and mechanobiology in the presence of the native matrix. Such approaches could be applicable to study the mechanisms of bone repair, whilst also enabling exploration of biomechanical cues. However, to date an ex vivo model of bone remodelling in cortical bone has not been developed. In this study, the objective was to develop an ex vivo model where cortical bone was subjected to cyclic strains to study the remodelling of bone. Materials and Methods. Ex vivo model of bone remodelling induced by cyclic loading: At the day of culling, beam-shape bovine bone samples were cut and preserved in PBS + 5% Pen/Strep + 2 mM L-Glut overnight at 37°C. Cyclic strains were applied with a three-point bend system to induce damage with a regime at 16.66 mm/min for 5,000 cycles in sterile PBS in Evolve® bags (maximum strain 6%). A control group was cultured under static conditions. Metabolic activity: Alamar Blue assays were performed after 1 and 7 days of ex vivo culture for each group (Static, Loaded) and normalized to weight. Bone remodelling: ALP activity was assessed in the media at day 1 and 7. After 24 hours cell culture conditioned media (CM) was collected from each group and stored at −80°C. RAW264.7 cells were cultured with CM for 6 days, after which the samples were stained for TRAP, to determine osteoclastogenesis, and imaged. Histomorphometry: Samples were cultured with calcein for 3 days to label bone formation between day 4 and 7. Fluorescent images were captured at day 7. μCT scanning was performed at 3 μm resolution after labelling samples with BaSO. 4. precipitate to quantify bone damage. Results. Bone was sectioned and cultured to maintain live osteoblasts and osteocytes. CM that was obtained 24 hours after cyclic loading and added to RAW264.7 cells cultures, resulted in significantly increased osteoclastogenic potential compared to that from static samples (4.245±1.65% vs 0.88±0.48%, p<0.001). Calcein and HE staining indicated the presence of structures similar to bone remodelling cones in both groups after 7 days of culture. Also, 7 days post-loading, matrix microdamage in the stimulated area, detected with the BaSO. 4. precipitate, were not significantly increased under the load point in loaded samples (0.11±0.05% of bone volume), while at the support areas it was significantly higher (0.2387±0.06%, p<0.001) compared to the static (0.062±0.02%). Conclusions. This study demonstrates that (1) cyclic strains applied on ex vivo bovine cortical bone successfully induced remodelling as characterized by the formation of bone resorption cones, along with an increase of osteoclast formation, and (2) there was an induction of microdamage post loading as shown by the significant increases in microdamage labelled. This supports previous in vivo studies with an increase in osteoclastogenesis up to 7 days post loading. This is the first evidence of the development of an ex vivo model to study osteon remodelling that could be applied to study bone physiology and repair

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

Aims. Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA. Methods. First, we obtained gene expression profiles of cartilage, synovium, subchondral bone, and meniscus from the Gene Expression Omnibus (GEO). Several datasets were standardized by merging and removing batch effects. Then, we used unsupervised clustering to divide OA into three subtypes. The gene ontology and pathway enrichment of three subtypes were analyzed. CIBERSORT was used to evaluate the infiltration of immune cells in different subtypes. Finally, OA-related genes were obtained from the Molecular Signatures Database for validation, and diagnostic markers were screened according to clinical characteristics. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of markers. Results. C1 subtype is mainly concentrated in the development of skeletal muscle organs, C2 lies in metabolic process and immune response, and C3 in pyroptosis and cell death process. Therefore, we divided OA into three subtypes: bone remodelling subtype (C1), immune metabolism subtype (C2), and cartilage degradation subtype (C3). The number of macrophage M0 and activated mast cells of C2 subtype was significantly higher than those of the other two subtypes. COL2A1 has significant differences in different subtypes. The expression of COL2A1 is related to age, and trafficking protein particle complex subunit 2 is related to the sex of OA patients. Conclusion. This study linked different tissues with gene expression profiles, revealing different molecular subtypes of patients with knee OA. The relationship between clinical characteristics and OA-related genes was also studied, which provides a new concept for the diagnosis and treatment of OA. Cite this article: Bone Joint Res 2023;12(12):702–711

Femoroacetabular impingement (FAI) results from a morphological deformity of the hip and is associated with osteoarthritis (OA). Increased bone mineral density (BMD) is observed in the antero-superior acetabulum rim where impingement occurs. It is hypothesized that the repeated abnormal contact leads to damage of the cartilage layer, but could also cause a bone remodelling response according to Wolff's Law. Thus the goal of this study was to assess the relationship between bone metabolic activity measured by PET and BMD measured in CT scans. Five participants with asymptomatic cam deformity, three patients with uni-lateral symptomatic cam FAI and three healthy controls were scanned in a 3T PET-MRI scanner following injection with [18F]NaF. Bone remodelling activity was quantified with Standard Uptake Values (SUVs). SUVmax was analyzed in the antero-superior acetabular rim, femoral head and head-neck junction. In these same regions, BMD was calculated from CT scans using the calibration phantom included in the scan. The relationship between SUVmax and BMD from corresponding regions was assessed using the coefficient of determination (R. 2. ) from linear regression. High bone activity was seen in the cam deformity and acetabular rim. SUVmax was negatively correlated with BMD in the antero-superior region of the acetabulum (R. 2. =0.30, p=0.08). SUVmax was positively correlated with BMD in the antero-superior head-neck junction of the femur (R. 2. =0.359, p=0.067). Correlations were weak in other regions. Elevated bone turnover was seen in patients with a cam deformity but the relationship to BMD was moderate. This study demonstrates a pathomechanism of hip degeneration associated with FAI deformities, consistent with Wolff's law and the proposed mechanical cause of hip degeneration in FAI. [18F]-NaF PET SUV may be a biomarker of degeneration, especially in early stages of degeneration, when joint preservation surgery is likely to be the most successful

The success of cementless orthopaedic implants relies on bony ingrowth and active bone remodelling. Much research effort is invested to develop implants with controllable surface roughness and internal porous architectures that encourage these biological processes. Evaluation of these implants requires long-term and costly animal studies, which do not always yield the desired outcome requiring iteration. The aim of our study is to develop a cost-effective method to prescreen design parameters prior to animal trials to streamline implant development and reduce live animal testing burden. Ex vivo porcine cancellous bone cylinders (n=6, Ø20×12mm) were extracted from porcine knee joints with a computer-numerically-controlled milling machine under sterile conditions within 4 hours of animal sacrifice. The bone discs were implanted with Ø6×12mm additive manufactured porous titanium implants and were then cultured for 21days. Half underwent static culture in medium (DMEM, 10% FBS, 1% antibiotics) at 37°C and 5% CO. 2. The rest were cultured in novel high-throughput stacked configuration in a bioreactor that simulated physiological conditions after surgery: the fluid flow and cyclic compression force were set at 10ml/min and 10–150 N (1Hz,5000 cycles/day) respectively. Stains were administered at days 7 and 14. Samples were evaluated with widefield microscopy, scanning electron microscopy (SEM) and with histology. More bone remodelling was observed on the samples cultured within the bioreactor: widefield imaging showed more remodelling at the boundaries between the implant-bone interface, while SEM revealed immature bone tissue integration within the pores of the implant. Histological analysis confirmed these results, with many more trabecular struts with new osteoid formation on the samples cultured dynamically compared to static ones. Ex vivo bone can be used to analyse new implant technologies with lower cost and ethical impact than animal trial. Physiological conditions (load and fluid flow) promoted bone ingrowth and remodelling