Aims

Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application.

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment.

Cite this article: Bone Joint Res 2024;13(12):725–740.

The December 2024 Research Roundup³⁶⁰ looks at: Skeletal muscle composition, power, and mitochondrial energetics in older men and women with knee osteoarthritis; Machine-learning models to predict osteonecrosis in patients with femoral neck fractures undergoing internal fixation; Aetiology of patient dissatisfaction following primary total knee arthroplasty in the era of robotic-assisted technology; Efficacy and safety of commonly used thromboprophylaxis agents following hip and knee arthroplasty; The COVID-19 effect continues; Nickel allergy in knee arthroplasty: does self-reported sensitivity affect outcomes?; Tranexamic acid use and joint infection risk in total hip and knee arthroplasty.

Aim. Swedish guidelines on antibiotic prophylaxis in arthroplasty surgery recommend cloxacillin in fixed doses that pay little attention to the patient's renal function and weight. Nevertheless, there are no studies on whether the resulting free prophylactic cloxacillin in vivo concentrations are optimal. We aimed to evaluate whether the current recommended prophylactic dosage of cloxacillin is adequate. Method. We performed a prospective two-centre study, measuring the free (active) cloxacillin concentrations in plasma throughout surgery, in patients subject to primary hip and knee prosthetic joint replacements, aiming at 100 patients per centre. To account for plasma-bone exposure differences, concentrations were considered adequate if twice the epidemiological cut-off value for cloxacillin concerning wild type Staphylococcus aureus whereas two-three times were labelled threshold values. The two enrolling hospitals are acute care hospitals in central Sweden, also performing 600 - 1200 primary hip and knee joint arthroplasties annually. All patients scheduled for elective primary hip or knee replacements from January 2022 to April 2024 were eligible for participation. Exclusion criteria were allergy towards penicillins, cognitive disorders leading to inability to sign informed consent, and an absence of interpreter in case of a patient not speaking Swedish or English. Results. We present results from the first 49 patients included. Four patients had free cloxacillin concentrations below cut-off (8.2%). These four cases had prolonged surgeries of 77-100 minutes. An additional 5/49 (10.2%) had threshold values. Conversely 5/49 (10.2%) cases had concentrations exceeding 15 times the needed. No cases with threshold or low cloxacillin concentrations were attributable to a lack of concerning timing and dosing of cloxacillin. All concentrations were above or equal to our cut-off at the start of surgery. Eighteen percent of patients were of normal of weight (BMI 18.5- 25). Of the rest 4% were morbidly obese (BMI >40), 41% obese (BMI 30-40) and 37% overweight (BMI 25-30). Twenty seven percent (43/159) had diabetes and 45% suffered cardiac disease. Conclusions. Some patients in our cohort had insufficient active cloxacillin levels at the end of prosthetic joint surgery. Previous studies indicate that insufficient prophylactic antibiotic concentrations might lead to an enhanced risk of prosthetic joint infections. Other patients were massively overdosed, leading to unnecessary ecological effects and potentially adverse reactions. As inadequate cloxacillin concentrations were not associated with a lack of compliance to current guidelines a change in practise might be needed. Our final results may help to determine how dosing should be adjusted

Introduction. Low back pain (LBP) is a worldwide leading cause of disability. This preclinical study evaluated the safety of a combined advanced therapy medicinal product developed during the European iPSpine project (#825925) consisting of mesendoderm progenitor cells (MEPC), derived from human induced pluripotent stem cells, in combination with a synthetic poly(N-isopropylacrylamide) hydrogel (NPgel) in an ovine intervertebral disc degeneration (IDD) model. Method. IDD was induced through nucleotomy in 4 adult sheep, 5 lumbar discs each (n=20). After 5 weeks, 3 alternating discs were treated with NPgel (n=6) or NPgel+MEPC (n=6). Before sacrifice, animals were subjected to: MRI of lumbar spines (disc height and Pfirmann grading); blood sampling (hematological, biochemical, metabolic and lymphocyte/monocytes immunological). After 3 months the sheep were sacrificed. The spines were processed for: macroscopic morphology (Thompson grading), microscopic morphology (Histological grading), and glycosaminoglycan content (GAG, DMMB Assay). Furthermore, at sacrifice biodistribution of human MEPC was assessed by Alu-sequences quantification (qPCR) from three tissue samples of heart, liver, spleen, brain, lungs, and kidneys, and PBMCs collected to assess activation of systemic immune cells. To each evaluation, appropriate statistical analysis was applied. Result. Flow cytometry showed no induction of systemic activation of T cells or monocytes. Alu quantification did not give detection of any cells in any organ. Disc height index was slightly increased in discs treated with NPgel+MEPC. Pfirmann's and Thompson's classification showed that treatment with NPgel or NPgel+MEPC gave no adverse reactions. Histological grading showed similar degeneration in vertebrae treated with NPgel+MEPC or with NPgel alone. The amount of GAG was significantly increased in the nucleus pulposus following treatment with NPgel+MEPC compared to NPgel alone, in which a decrease was observed compared to untreated discs in both nucleus pulposus and annulus fibrosus. Conclusion. This study showed the safety of both NPgel+MEPC and NPgel treatments

Aims

The incidence of limb fractures in patients living with HIV (PLWH) is increasing. However, due to their immunodeficiency status, the operation and rehabilitation of these patients present unique challenges. Currently, it is urgent to establish a standardized perioperative rehabilitation plan based on the concept of enhanced recovery after surgery (ERAS). This study aimed to validate the effectiveness of ERAS in the perioperative period of PLWH with limb fractures.

Aims

A local injection may be used as an early option in the treatment of Morton’s neuroma, and can be performed using various medications. The aim of this study was to compare the effects of injections of hyaluronic acid compared with corticosteroid in the treatment of this condition.

The October 2024 Hip & Pelvis Roundup³⁶⁰ looks at: Does the primary surgical approach matter when choosing the approach for revision total hip arthroplasty?; Time to achieve the minimal clinically important difference in primary total hip arthroplasty: comparison of anterior and posterior surgical approaches; To scope or not to scope: arthroscopy as an adjunct to PAO does not provide better clinical outcomes at one year than PAO alone; Re-exploring horizons in hip resurfacing: two-year results of a ceramic-on-ceramic hip resurfacing; Association between tranexamic acid and decreased periprosthetic joint infection risk in patients undergoing total hip and knee arthroplasty; Octogenarians fare well: in revision for infection age is not a bar.

Aims

Knee osteoarthritis (OA) is characterized by a chronic inflammatory process involving multiple cytokine pathways, leading to articular cartilage degeneration. Intra-articular therapies using pharmaceutical or autologous anti-inflammatory factors offer potential non-surgical treatment options. Autologous protein solution (APS) is one such product that uses the patient’s blood to produce a concentrate of cells and anti-inflammatory cytokines. This study evaluated the effect of a specific APS intra-articular injection (nSTRIDE) on patient-reported outcome measures compared to saline in moderate knee OA.

In 1997 the Birmingham Hip Resurfacing was introduced to address the needs of young active patients. Alternative designs were introduced to try and improve wear performance. The aim of this study was a comparative cohort study of two types of metal-on-metal bearing to determine the mechanism of failure at 15 years. The study reviewed 91 Brimingham Hip Resurfacings (BHR) (Smith and Nephew) and 715 DUROM hip resurfacing (Zimmer) procedures in prior to 2009. Failure was defined as revision of either component for any reason. Kaplan-Meyer survivorship analysis performed. Routine follow-up with serum metal ion levels and radiographs. Mean follow-up was 17.9 years (range 15.2 – 25.1). The mean age at operation was 51.6 years (SD 8.6, range 20.7 to 70.2), including 299 women (37.1%). The Birmingham resurfacing demonstrated 92.3% survivorship at 15 years (SE 2.8, 95% CI 3.9 – 7.8) and 90.0% at latest follow-up (SE 3.5, 95% CI 4.9 to 9.4). By comparison, the DUROM survivorship at 15 years was 89.1% at 15 years (SE 1.2, 95% CI 2.0 to 2.5) and 87.4% (SE 1.3, 95% CI 2.5 to 2.3) at latest follow-up. There was no statistically significant difference in survivorship between groups (p= 0.32). Survival in male patients was 92.7% compared to 80.0% in females. The reported failures occurred from Adverse Reaction to Metal Debris (32 patients), periprosthetic femoral neck fracture (6) and aseptic loosening (41), PJI (12) and undiagnosed pain (6). The mean cobalt and chromium levels at last follow-up were 33.4 nmol/L and 36.5 nmol/L respectively. This study demonstrates two differently designed metal-on-metal hip resurfacing provided a durable alternative to total hip replacement, particularly in younger male patients with osteoarthritis. Differences in design did determine the reason for revision with acetabular fixation being one of the principal failure mechanisms for the DUROM compared to elevated ion levels

Aims

During total knee replacement (TKR), surgeons can choose whether or not to resurface the patella, with advantages and disadvantages of each approach. Recently, the National Institute for Health and Care Excellence (NICE) recommended always resurfacing the patella, rather than never doing so. NICE found insufficient evidence on selective resurfacing (surgeon’s decision based on intraoperative findings and symptoms) to make recommendations. If effective, selective resurfacing could result in optimal individualized patient care. This protocol describes a randomized controlled trial to evaluate the clinical and cost-effectiveness of primary TKR with always patellar resurfacing compared to selective patellar resurfacing.

Aims

Intra-articular (IA) injection may be used when treating hip osteoarthritis (OA). Common injections include steroids, hyaluronic acid (HA), local anaesthetic, and platelet-rich plasma (PRP). Network meta-analysis allows for comparisons between two or more treatment groups and uses direct and indirect comparisons between interventions. This network meta-analysis aims to compare the efficacy of various IA injections used in the management of hip OA with a follow-up of up to six months.

Aims. The Birmingham Hip Resurfacing (BHR) was introduced in 1997 to address the needs of young active patients using a historically proven large-diameter metal-on-metal (MoM) bearing. A single designer surgeon’s consecutive series of 130 patients (144 hips) was previously reported at five and ten years, reporting three and ten failures, respectively. The aim of this study was to extend the follow-up of this original cohort at 25 years. Methods. The study extends the reporting on the first consecutive 144 resurfacing procedures in 130 patients for all indications. All operations were undertaken between August 1997 and May 1998. The mean age at operation was 52.1 years (SD 9.93; 17 to 76), and included 37 female patients (28.5%). Failure was defined as revision of either component for any reason. Kaplan-Meier survival analysis was performed. Routine follow-up with serum metal ion levels, radiographs, and Oxford Hip Scores (OHSs) was undertaken. Results. Overall implant survival was 83.50% (95% confidence interval (CI) 0.79 to 0.90) at 25 years, and the number at risk was 79. Survival in male patients at 25 years was 89.5% (95% CI 0.83 to 0.96) compared to 66.9% for female patients (95% CI 0.51 to 0.83). Ten additional failures occurred in the period of ten to 25 years. These involved an adverse reaction to metal debris in four patients, a periprosthetic femoral neck fracture affecting five patients, and aseptic loosening in one patient. The median chromium levels were 49.50 nmol/l (interquartile range (IQR) 34 to 70), and the median cobalt serum levels were 42 nmol/l (IQR 24.50 to 71.25). The median OHS at last follow-up was 35 (IQR 10 to 48). During the 25-year study period, 29 patients died. Patient survival at 25 years was 75.10% (95% CI 0.67 to 0.83). Conclusion. This study demonstrates that MoM hip resurfacing using the BHR provides a durable alternative to total hip arthroplasty (THA), particularly in younger male patients with osteoarthritis wishing to maintain a high level of function. These results compare favourably to the best results for THAs. Cite this article: Bone Joint J 2024;106-B(6):540–547

Aims

This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection.

Aims

Gram-negative infections are associated with comorbid patients, but outcomes are less well understood. This study reviewed diagnosis, management, and treatment for a cohort treated in a tertiary spinal centre.

Aims

Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI.

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The aims of this study were to determine the success of a reconstruction algorithm used in major acetabular bone loss, and to further define the indications for custom-made implants in major acetabular bone loss.

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Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium.

Aims

Is it feasible to conduct a definitive multicentre trial in community settings of corticosteroid injections (CSI) and hydrodilation (HD) compared to CSI for patients with frozen shoulder? An adequately powered definitive randomized controlled trial (RCT) delivered in primary care will inform clinicians and the public whether hydrodilation is a clinically and cost-effective intervention. In this study, prior to a full RCT, we propose a feasibility trial to evaluate recruitment and retention by patient and clinician willingness of randomization; rates of withdrawal, crossover and attrition; and feasibility of outcome data collection from routine primary and secondary care data.

Aims. In metal-on-polyethylene (MoP) total hip arthroplasty (THA), large metal femoral heads have been used to increase stability and reduce the risk of dislocation. The increased size of the femoral head can, however, lead to increased taper corrosion, with the release of metal ions and adverse reactions. The aim of this study was to investigate the relationship between the size of the femoral head and the levels of metal ions in the blood in these patients. Methods. A total of 96 patients were enrolled at two centres and randomized to undergo MoP THA using either a 32 mm metal head or a femoral head of between 36 mm and 44 mm in size, being the largest possible to fit the thinnest available polyethylene insert. The levels of metal ions and patient-reported outcome measures (Oxford Hip Score, University of California, Los Angeles Activity Scale) were recorded at two and five years postoperatively. Results. At five years, the median levels of chromium, cobalt, and titanium were 0.5 μg/l (interquartile range (IQR) 0.50 to 0.62), 0.24 μg/l (IQR 0.18 to 0.30), and 1.16 μg/l (IQR 1.0 to 1.68) for the 32 mm group, and 0.5 μg/l (IQR 0.5 to 0.54), 0.23 μg/l (IQR 0.17 to 0.39), and 1.30 μg/l (IQR 1 to 2.05) for the 36 mm to 44 mm group, with no significant difference between the groups (p = 0.825, p = 1.000, p = 0.558). There were increased levels of metal ions at two years postoperatively in seven patients in the 32 mm group, compared with four in the 36 mm to 44 mm group, and at five years postoperatively in six patients in the 32 mm group, compared with seven in the 36 mm to 44 mm group. There was no significant difference in either the OHS (p = 0.665) or UCLA (p = 0.831) scores between patients with or without an increased level of metal ions. Conclusion. In patients who underwent MoP THA, we found no differences in the levels of metal ions five years postoperatively between those with a femoral head of 32 mm and those with a femoral head of between 36 mm and 44 mm, and no corrosion-related revisions. As taper corrosion can start after five years, there remains a need for longer-term studies investigating the relationship between the size of the femoral head size and corrosion in patients undergoing MoP THA. Cite this article: Bone Joint J 2024;106-B(3 Supple A):31–37