Aims

Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS.

Aims

Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies.

Osteoporosis is a common problem in postmenopausal women and the elderly. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that primarily activates glucocorticoids (GCs) in vivo, which is a considerable potential target as treatment for osteoporosis. Previous studies have demonstrated its effect on osteogenesis, and our study aimed to demonstrate its effect on osteoclast activation.

In vivo, we used 11β-HSD1 knock-off (KO) and C57BL6/J mice to undergo the ovariectomy-induced osteoporosis (OVX). In vitro, In vivo, We used 11β-HSD1 knockoff (KO) and C57BL6/J mice to undergo the ovariectomy-induced osteoporosis (OVX). In vitro, bone marrow-derived macrophages (BMM) and bone marrow mesenchymal stem cell (BMSC) of KO and C57BL6/J mice were extracted to test their osteogenic and osteoclastic abilities. We then created osteoclastic 11β-HSD1 elimination mice (Ctsk::11β-HSD1fl/fl) and treated them with OVX. Micro-CT analysis, H&E, immunofluorescence staining, and qPCR were performed. Finally, we conducted the high-throughput sequencing to find out 11β-HSD1 and osteoclast activation related genes.

We collected 6w samples after modeling. We found that KO mice were resistant to loss of bone trabeculae. The same effect was observed in osteoclastic 11β-HSD1 elimination mice. Meanwhile, BVT-2733, a classic inhibitor of 11β-HSD1, inhibited the osteoclast effect of cells without affecting osteogenic effect in vitro. High-throughput sequencing suggested that glucocorticoid receptor (GR) may play a key role in the activation of osteoclasts, which was verified by immunofluorescence staining and WB in vivo and in vitro.

In the process of osteoporosis, 11β-HSD1 expression of osteoclasts is abnormally increased, which may be a new target for inhibiting osteoclast activation and treating osteoporosis.

Though dentin matrix protein 1 (Dmp1) is known to play critical role in mediating bone mineralization, it has also been validated to be expressed in brain and helps maintain blood brain barrier (BBB). Our study aims to clarify the expression pattern of Dmp1 in mouse brain and explore whether intercellular mitochondrial transfer occurs between Dmp1 positive astrocytes (DPAs) and endothelial cells, and thus acting as a mechanism in maintaining BBB during aging.

Single cell RNA sequencing (scRNAseq) of 1 month, 6 month, and 20 month old mice brain (n=1, respectively) was employed to identify Dmp1 positive cell types. Dmp1^Cre-mGmT and Dmp1^Cre-COX8a fluorescent mice were generated to visualize DPAs and investigate their mitochondrial activities. A 3D noncontact coculture system and mitochondrial transplantation were applied to study the role of mitochondrial transfer between astrocytes and bEnd.3 endothelial cells. Dmp1^Cre-Mfn2^f/f mice were generated by depleting the ER-mitochondria tethering protein Mfn2 in DPAs.

Dmp1 was mainly expressed in astrocytes at different ages. GO analysis revealed that cell projection and adhesion of DPAs were upregulated. Confocal imaging on Dmp1^Cre-mGmT mice indicated that DPAs are a cluster of astrocytes that closely adhere to blood vessels (n=3). Bioinformatics analysis revealed that mitochondrial activity of DPAs were compromised during aging. Enriched scRNAseq of fluorescent cells from Dmp1^Cre-COX8a mice (n=2) and immunofluorescent imaging (n=3) validated the acquisition of extrinsic mitochondria in endothelial cells. 3D coculture of astrocytes and bEnd.3 and direct mitochondrial transplantation revealed the rescue effect of mitochondrial transfer on damaged bEnd.3. BBB was impaired after depleting Mfn2 in DPAs, expressing a similar phenotype with aging brain.

Astrocytes that express Dmp1 play a significant role in maintaining BBB via transferring mitochondria to vascular endothelial cells. Compromised mitochondrial transfer between DPAs and endothelial cells might be the potential mechanism of impaired BBB during aging.

Lumbar diseases have become a major problem affecting human health worldwide. Conservative treatment of lumbar diseases is difficult to achieve ideal results, and surgical treatment of trauma, complications, it is imperative to develop a new treatment method. This study aims to explore the regulatory mechanism of cartilage endplate ossification caused by abnormal stress, and design intervention targets for this mechanism, so as to provide theoretical reference for the prevention and treatment of lumbar degeneration.

In vivo, we constructed spinal instability model in mice. In vitro, we used a mechanical tensile machine to simulate the abnormal stress conditions of the endplate cartilage cells. Through the high-throughput sequencing, we found the enrichment of Hippo signaling pathway. As YAP is a key protein in the Hippo signaling pathway, we then created cartilaginous YAP elimination mice (Col2::YAPfl/fl). The lumbar spine model was constructed again in these mice for H&E, SOFG and immunofluorescence staining. In vitro lentivirus was used to knock out YAP, immunofluorescence staining, WB and qPCR were performed. Finally, we conducted therapeutic experiments by using YAP agonist and AAV5 carrying YAP plasmids.

We collected 8w samples from C57/BL6 mice after modeling. We found ossification of the endplate in mice similar to human disc degeneration. High-throughput sequencing of stretched cells demonstrated high enrichment of the Hippo signaling pathway. By immunofluorescence staining, it was confirmed that Col-II decreased and Col-X gradually increased in the endplate cartilage of mice. This was also confirmed at 7 days after an in vitro stretch of 5% and 12%. Meanwhile, we found that cartilaginous YAP elimination mice developed very severe endplate degeneration. However, the endplate was well protected by intraperitoneal injection of YAP agonist or AAV5-YAP endplate injection, and the results in vitro were consistent with that.

In the process of cartilaginous ossification, abnormal stress regulates Col10a1 to promote cartilage endplate ossification through Hippo signaling pathway mediated YAP, and we expect to find potential drug targets for treatment through this mechanism.

Osteoarthritis (OA) is a degenerative disease resulting from progressive joint destruction caused by many factors. Its pathogenesis is complex and has not been elucidated to date. Advanced glycation end products (AGEs) are a series of irreversible and stable macromolecular complexes formed by reducing sugar with protein, lipid, and nucleic acid through a non-enzymatic glycosylation reaction (Maillard reaction). They are an important indicator of the degree of ageing. Currently, it is considered that AGEs accumulation in vivo is a molecular basis of age-induced OA, and AGEs production and accumulation in vivo is one of the important reasons for the induction and acceleration of the pathological changes of OA. In recent years, it has been found that AGEs are involved in a variety of pathological processes of OA, including extracellular matrix degradation, chondrocyte apoptosis, and autophagy. Clearly, AGEs play an important role in regulating the expression of OA-related genes and maintaining the chondrocyte phenotype and the stability of the intra-articular environment. This article reviews the latest research results of AGEs in a variety of pathological processes of OA, to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment.

Cite this article: Bone Joint Res 2022;11(5):292–300.

Aims

The diagnosis of periprosthetic joint infection (PJI) has always been challenging. Recently, D-dimer has become a promising biomarker in diagnosing PJI. However, there is controversy regarding its diagnostic value. We aim to investigate the diagnostic value of D-dimer in comparison to ESR and CRP.

Aims

High body mass index (BMI) is associated with increased rates of complications in primary total hip arthroplasty (THA), but less is known about its impact on cost. The effects of low BMI on outcomes and cost are less understood. This study evaluated the relationship between BMI, inpatient costs, complications, readmissions, and utilization of post-acute services.

Aims

Many biomechanical studies have shown that the weakest biomechanical point of a rotator cuff repair is the suture-tendon interface at the medial row. We developed a novel double rip-stop (DRS) technique to enhance the strength at the medial row for rotator cuff repair. The objective of this study was to evaluate the biomechanical properties of the DRS technique with the conventional suture-bridge (SB) technique and to evaluate the biomechanical performance of the DRS technique with medial row knots.

Background

Core decompression (CD) is effective to relieve pain and delay the advent of total hip arthroplasty (THA) for osteonecrosis of the femoral head (ONFH). However, the influence of CD on the subsequent THA has not been determined yet.

Objectives

The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA).

Aims

The aim of this study was to describe the technique of distraction osteogenesis followed by arthrodesis using internal fixation to manage complex conditions of the ankle, and to present the results of this technique.

Bone and joint infections are not only common but their management can be technically complex. They carry significant healthcare costs and are a daunting experience for patients [1]. Frequently, multiple operations are required in order to treat the infection. Each surgical intervention usually results in greater bone loss, worsening skin and soft tissue scarring and increasingly diverse and resistant micro- organisms [2].

Specialist bone infection units involving highly integrated orthopaedic and plastic surgery, as well as infection physicians, may improve patient outcomes [3–4]. However, it is difficult to determine the hierarchy of factors contributing to outcome of treatment. This problem is confounded by a lack of structured, prospective data collection in many units around the world.

In 2014, we designed a modular database which allows collection of patients’ details, components of the disease, the treatment, microbiology, histology, clinical outcome and patient-reported outcome measures (PROMS). The registry was implemented in November 2014 and has already demonstrated its function as a Hospital-wide service evaluation tool.

Over 200 patients have been referred to the unit and their baseline demographic information registered. Their progress through the bone infection unit patient pathway is prospectively monitored with use of the registry and data collection ongoing. We aim to present the preliminary clinical outcomes of these 200 patients including surgical procedures performed, key microbiology results, antibiotic treatment regimens and patient reported outcomes.

Our goal is to demonstrate that a bone infection registry is an integral part of infection management clinical practice. It can be used for designing service provision, assist in allocating healthcare resources and expand the evidence base for specialist bone infection units in managing complex orthopaedic infections.

There have been several studies examining the association between the morphological characteristics seen in acetabular dysplasia and the incidence of the osteoarthritis (OA).

However, most studies focus mainly on acetabular morphological analysis, and few studies have scrutinised the effect of femoral morphology. In this study we enrolled 36 patients with bilateral acetabular dysplasia and early or mid-stage OA in one hip and no OA in the contralateral hip. CT scans were performed from the iliac crest to 2 cm inferior to the tibial tuberosity, and the morphological characteristics of both acetabulum and femur were studied.

In addition, 200 hips in 100 healthy volunteer Chinese adults formed a control group. The results showed that the dysplastic group with OA had a significantly larger femoral neck anteversion and a significantly shorter abductor lever arm than both the dysplastic group without OA and the controls. Femoral neck anteversion had a significant negative correlation with the length of the abductor lever arm and we conclude that it may contribute to the development of OA in dysplastic hips.

Cite this article: Bone Joint J 2014; 96-B:1586–93.

In developmental dysplasia of the hip (DDH), a bone defect is often observed superior to the acetabulum after the reconstruction at the level of the true acetabulum during total hip replacement (THR). However, the essential amount of uncemented acetabular component coverage required for a satisfactory outcome remains controversial. The purpose of this study was to assess the stability and function of acetabular components with a lack of coverage > 30% (31% to 50%). A total of 760 DDH patients underwent THR with acetabular reconstruction at the level of the true floor. Lack of coverage above the acetabular component of > 30% occurred in 56 patients. Intra-operatively, autogenous morcellised bone grafts were used to fill the uncovered portion. Other than two screws inserted through the acetabular shell, no additional structural supports were used in these hips. In all, four patients were lost to follow-up. Therefore, 52 patients (52 hips, 41 women and 11 men) with a mean age of 60.1 years (42 to 78) were available for this study at a mean of 4.8 years (3 to 7). There were no instances of prosthesis revision or marked loosening during the follow-up. The Harris hip score improved from a mean of 40.7 points (sd 12.2) pre-operatively to 91.1 (sd 5.0) at the last follow-up. Radiological analysis with medical imaging software allowed us to calculate the extent of the uncoverage in terms of the uncovered arc of the implant as viewed on the anteroposterior pelvic radiograph. From this we propose that up to 17 mm of lateral undercoverage in the presence of a stable initial implantation in the presence of bone autografting, with an inclination angle of the acetabular component between 40° and 55°, is acceptable. This represents undercoverage of ≤ 50%.

Cite this article: Bone Joint J 2013;95-B:1178–83.

Background

The British Orthopaedic Association Standards for Trauma (BOAST) for peripheral nerve injuries¹ states:

This study investigated whether this standard was met for patients with upper limb trauma at a busy London Accident and Emergency (A&E) Department.

Study design: We conducted a prospective cohort study of 448 patients with a variety of spinal metastases.

Introduction: In the pathogenesis of steroid-associated femoral head necrosis only intra- and extravascular factors have been discussed. This study investigated the effect of long term glucocorticoid treatment on contraction of intraosseous femoral head arteries in a porcine model.

Materials and Methods: From 24 immature female Danish Landrace pigs from 12 litters, 12 animals received 100 mg methylprednisolone daily for 3 months. Their 12 sister pigs served as controls and received no steroids. Resistance arteries (diameter approximately 250 μm) were isolated from the femoral head epiphyseal cancellous bone and mounted as ring preparations on a small vessel myograph for measurement of isometric force development.

Results: Increasing doses of endothelin-1 evoked significantly stronger vasoconstriction after 3 months of methylprednisolone treatment. The vasocontractory response to increasing doses of noradrenaline was not altered by the previous methylprednisolone treatment. After submaximal precontraction by noradrenaline, vasorelaxation by bradykinin was not altered by methylprednisolone treatment.

Discussion: The vasocontractory response of isolated intraosseous femoral head epiphyseal arteries to endothelin-1 after long term glucocorticoid treatment in the pig was enhanced. Enhanced contraction of FH lateral epiphyseal arteries can diminish femoral head blood flow as vessel diameter decreases. This may be a relevant cofactor in the early pathogenesis of steroid-associated femoral head necrosis.