Aims. Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis. Methods. Blood and femoral bone marrow suspension IL-19 levels were first measured in the lipopolysaccharide (LPS)-induced bone loss model. Small interfering RNA (siRNA) was applied to knock down IL-19 for further validation. Thereafter, osteoclast production was stimulated with IL-19 in combination with mouse macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The effect of IL-19 was subsequently evaluated using tartrate-resistant acid phosphatase (TRAP) staining and quantitative real-time polymerase chain reaction (RT-qPCR). The effect of IL-19 on osteoprotegerin (OPG) was then assessed using in vitro recombinant IL-19 treatment of primary osteoblasts and MLO-Y4 osteoblast cell line. Finally, transient transfection experiments and chromatin immunoprecipitation (ChIP) experiments were used to examine the exact mechanism of action. Results. In the LPS-induced bone loss mouse model, the levels of IL-19 in peripheral blood serum and femoral bone marrow suspension were significantly increased. The in vivo results indicated that global IL-19 deletion had no significant effect on RANKL content in the serum and bone marrow, but could increase the content of OPG in serum and femoral bone marrow, suggesting that IL-19 inhibits OPG expression in bone marrow mesenchymal stem cells (BMSCs) and thus increases bone resorption. Conclusion. IL-19 promotes bone resorption by suppressing OPG expression in BMSCs in a LPS-induced bone loss mouse model, which highlights the potential benefits and side effects of IL-19 for future clinical applications. Cite this article: Bone Joint Res 2023;12(11):691–701

Aims. Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice. Methods. We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR). Results. Local delivery of NF-κB decoy ODN in vivo increased osteogenesis in males, but not females, in the presence of chronic inflammation induced by cPE. Bone resorption activity was decreased in both sexes. In vitro osteogenic and osteoclastic differentiation assays during inflammatory conditions did not reveal differences among the groups. Receptor activator of nuclear factor kappa Β ligand (Rankl) gene expression by osteoblasts was significantly decreased only in males when treated with ODN. Conclusion. We demonstrated that NF-κB decoy ODN increased osteogenesis in male mice and decreased bone resorption activity in both sexes in preclinical models of chronic inflammation. NF-κB signalling could be a therapeutic target for chronic inflammatory diseases involving bone, especially in males. Cite this article: Bone Joint Res 2024;13(1):28–39

A heavy infiltrate of foreign-body macrophages is commonly seen in the fibrous membrane which surrounds an aseptically loose cemented implant. This is in response to particles of polymethylmethacrylate (PMMA) bone cement and other biomaterials. We have previously shown that monocytes and macrophages responding to particles of bone cement are capable of differentiating into osteoclastic cells which resorb bone. To determine whether the radio-opaque additives barium sulphate (BaSO. 4. ) and zirconium dioxide (ZrO. 2. ) influence this process, particles of PMMA with and without these agents were added to mouse monocytes and cocultured with osteoblast-like cells on bone slices. Osteoclast differentiation, as shown by the presence of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and lacunar bone resorption, was observed in all cocultures. The addition of PMMA alone to these cocultures caused no increase in TRAP expression or bone resorption relative to control cocultures. Adding PMMA particles containing BaSO. 4. or ZrO. 2. , however, caused an increase in TRAP expression and a highly significant increase in bone resorption. Particles containing BaSO. 4. were associated with 50% more bone resorption than those containing ZrO. 2. . Our results suggest that radio-opaque agents in bone cement may contribute to the bone resorption of aseptic loosening by enhancing macrophage-osteoclast differentiation, and that PMMA containing is BaSO. 4. likely to be associated with more osteolysis than that containing ZrO. 2.

We investigated the possibility that the macrophages which are seen around implants may stimulate bone resorption and cause loosening. We found that macrophages release mediators that stimulate bone resorption, and that the amount of resorption increased by between 2.5 and 10 times when the macrophages adhered to a foreign surface. This bone resorption depended on the surface energy and roughness of the foreign surface, varying with these physical properties rather than with the chemical nature of the material. It is concluded that loosening of orthopaedic implants is likely to be influenced by the surface energy and roughness of the implant

We investigated in vitro a mechanism by which particulate debris may induce bone resorption and cause implant loosening. We first studied two standard particles: latex, which is considered to be inert, and zymosan, which is inflammatory. Macrophages that phagocytosed either particle became activated, and stimulated 15 times as much bone resorption as did control macrophages. For activation to occur, 100 times more latex than zymosan had to be phagocytosed. We also found that bone cement and polyethylene particles activated macrophages in a similar manner, and that the necessary amounts of these were intermediate between those of latex and zymosan. None of the particles were toxic. It was concluded that implant loosening may result from bone resorption stimulated by mediators released by macrophages that have phagocytosed particles of bone cement or polyethylene

Calvaria from six-day-old infant mice were grown on a grid culture in a chemically defined medium under varying oxygen tensions. Quantitative isotope studies demonstrated a linear association between bone resorption and oxygen tension in the physiological range. This result was supported by histological, histochemical and vital staining experiments. The clinical finding of osteoporosis in areas of hyperaemia could therefore be attributed to a rise in oxygen tension causing increased bone resorption

Using a rat model, we created a bone-to-titanium interface and applied phagocytosable high-density polyethylene pArticles between the bone and implant, either initially or when the interface had matured. No fibrous membrane developed and no bone resorption was found. If sliding movements were initiated at the interface after two weeks, there was formation of a fibrous membrane. The additional application of pArticles did not change the thickness of the membrane, and there were only minor qualitative changes. Creation of a membrane by movement followed by cessation of movement and the application of pArticles caused the membrane to persist, whereas in a pArticle-free control group bone-to-metal contact was re-established. Our findings suggest that mechanical stimuli are of primary importance for prosthetic loosening, and that pArticles may modulate the later stages of the loosening process

We reviewed at a minimum elapsed time of five years a consecutive series of 143 primary Exeter hip replacements in which matt-surfaced femoral stems had been used. Twenty-five patients had died and six stems and two sockets had been revised before follow-up. The remaining 110 hips were all examined clinically and radiographically. In 15 hips there were radiographic signs of definite loosening of the stem and in eight suspected loosening. The acetabulum was loose in four hips. In another eight hips localised bone resorption was present without signs of loosening. Half the patients with loosening or localised bone resorption had mild pain or no pain at all. The late complication rate with the matt-surfaced Exeter femoral stem is unacceptably high

Aims

The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice.

Wear particles commonly used for experiments may carry adherent endotoxin on their surfaces, which may be responsible for the observed effects. In this study, we attached titanium plates to the tibiae of 20 rats. After osseointegration, endotoxin-contaminated or uncontaminated high-density-polyethylene (HDPE) particles were applied. Contaminated specimens showed a dramatic resorption of bone after seven days but new bone filled the site again at 21 days. Uncontaminated specimens showed no resorption. In 18 rats we implanted intramuscularly discs of ultra-high-molecular-weight polyethylene (UHMWPE) with baseline or excess contamination of endotoxin. Excess endotoxin disappeared within 24 hours and the amount of endotoxin remained at baseline level (contamination from production). Uncontaminated titanium discs did not adsorb endotoxin in vivo. The endotoxin was measured by analytical chemistry. Locally-applied endotoxin stimulated bone resorption similarly to that in experiments with wear particles. Endotoxin on the surface of implants and particles appeared to be inactivated in situ. A clean implant surface did not adsorb endotoxin. Our results suggest that endotoxin adhering to orthopaedic implants is not a major cause for concern

Inadequate bone stock is often found in revision surgery of femoral components of total knee replacements. Our aim was to test the hypothesis that these remodelling patterns can be explained by stress shielding, and that prosthetic bonding characteristics affect maintenance of bone mass. We made a three-dimensional finite-element model of an average male femur with a cemented femoral knee component. This model was integrated with iterative remodelling procedures. Two extreme prosthetic bonding conditions were analysed and gradual changes in bone density were calculated. The long-term bone loss under the femoral knee component resembled clinical findings which confirms the hypothesis that stress shielding can cause distal femoral bone loss. Our study predicts, contrary to clinical findings, that an equilibrium situation is not reached after two years, but that bone resorption may continue. This hidden bone loss may be so drastic that large reconstructions are needed at the time of revision

Matrix metalloproteinases (MMPs) may have a role in the process of aseptic loosening. Doxycycline has been shown to inhibit MMPs. Our aim was to investigate the potential pharmacological effect of doxycycline on aseptic loosening. We used radiolabelled mouse calvariae cultured with human interface membrane cells from aseptically loosened hips. Bone resorption was confirmed in this model. The effect of doxycycline was assessed by culturing dead radiolabelled bone discs with cells from the interface membrane with doxycycline. The control group consisted of the same culture system without doxycycline. Supernatant . 45. calcium and the total . 45. calcium remaining in the bone discs at the completion of the culture were used to measure osteolysis. We found that doxycycline can inhibit osteolysis at the interface membrane of aseptically loosened hips. This may have therapeutic implications for the treatment of patients with aseptic loosening of total joint replacements

Aims

It has been hypothesized that proximal radial neck resorption (PRNR) following press-fit radial head arthroplasty (RHA) is due to stress-shielding. We compared two different press-fit stems by means of radiographs to investigate whether the shape and size of the stems are correlated with the degree of PRNR.

Aims

Surgeons and most engineers believe that bone compaction improves implant primary stability without causing undue damage to the bone itself. In this study, we developed a murine distal femoral implant model and tested this dogma.

Peri-prosthetic osteolysis and subsequent aseptic loosening is the most common reason for revising total hip replacements. Wear particles originating from the prosthetic components interact with multiple cell types in the peri-prosthetic region resulting in an inflammatory process that ultimately leads to peri-prosthetic bone loss. These cells include macrophages, osteoclasts, osteoblasts and fibroblasts. The majority of research in peri-prosthetic osteolysis has concentrated on the role played by osteoclasts and macrophages. The purpose of this review is to assess the role of the osteoblast in peri-prosthetic osteolysis.

In peri-prosthetic osteolysis, wear particles may affect osteoblasts and contribute to the osteolytic process by two mechanisms. First, particles and metallic ions have been shown to inhibit the osteoblast in terms of its ability to secrete mineralised bone matrix, by reducing calcium deposition, alkaline phosphatase activity and its ability to proliferate. Secondly, particles and metallic ions have been shown to stimulate osteoblasts to produce pro inflammatory mediators in vitro. In vivo, these mediators have the potential to attract pro-inflammatory cells to the peri-prosthetic area and stimulate osteoclasts to absorb bone. Further research is needed to fully define the role of the osteoblast in peri-prosthetic osteolysis and to explore its potential role as a therapeutic target in this condition.

Cite this article: Bone Joint J 2013;95-B:1021–5.

Aims

The primary aim of this study was to compare the wear properties of vitamin E-diffused, highly crosslinked polyethylene (VEPE) and one formulation of moderately crosslinked and mechanically annealed ultra-high molecular weight polyethylene (ModXLPE) in patients five years after primary total hip arthroplasty (THA). The secondary aim was to assess the clinical results of patients treated with VEPE by evaluating patient-reported outcome measures (PROMs), radiological evidence of fixation, and the incidence of mechanical failure.

Aims

The aim of this study was to evaluate the clinical and radiological outcome of using an anatomical short-stem shoulder prosthesis to treat primary osteoarthritis of the glenohumeral joint.

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. Methods. Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20). Results. PJI specimens exhibited a higher bone volume, thickened trabeculae, and increased osteoid parameters compared to both control groups, suggesting an accelerated bone turnover with sclerotic microstructure. On the cellular level, osteoblast and osteoclast parameters were markedly increased in the PJI cohort. Furthermore, a positive association between serum (CRP) but not synovial (white blood cell (WBC) count) inflammatory markers and osteoclast indices could be detected. Comparison between different pathogens revealed increased osteoclastic bone resorption parameters without a concomitant increase in osteoblasts in bone specimens from patients with Staphylococcus aureus infection, compared to those with detection of Staphylococcus epidermidis and Cutibacterium spp. Conclusion. This study provides insights into the local bone metabolism in chronic PJI, demonstrating osteosclerosis with high bone turnover. The fact that Staphylococcus aureus was associated with distinctly increased osteoclast indices strongly suggests early surgical treatment to prevent periprosthetic bone alterations. Cite this article: Bone Joint Res 2023;12(10):644–653

Bone defects are frequently observed in anterior shoulder instability. Over the last decade, knowledge of the association of bone loss with increased failure rates of soft-tissue repair has shifted the surgical management of chronic shoulder instability. On the glenoid side, there is no controversy about the critical glenoid bone loss being 20%. However, poor outcomes have been described even with a subcritical glenoid bone defect as low as 13.5%. On the humeral side, the Hill-Sachs lesion should be evaluated concomitantly with the glenoid defect as the two sides of the same bipolar lesion which interact in the instability process, as described by the glenoid track concept. We advocate adding remplissage to every Bankart repair in patients with a Hill-Sachs lesion, regardless of the glenoid bone loss. When critical or subcritical glenoid bone loss occurs in active patients (> 15%) or bipolar off-track lesions, we should consider anterior glenoid bone reconstructions. The techniques have evolved significantly over the last two decades, moving from open procedures to arthroscopic, and from screw fixation to metal-free fixation. The new arthroscopic techniques of glenoid bone reconstruction procedures allow precise positioning of the graft, identification, and treatment of concomitant injuries with low morbidity and faster recovery. Given the problems associated with bone resorption and metal hardware protrusion, the new metal-free techniques for Latarjet or free bone block procedures seem a good solution to avoid these complications, although no long-term data are yet available. Cite this article: Bone Joint J 2024;106-B(10):1100–1110

Aims. The aim of this study was to analyze how proximal radial neck resorption (PRNR) starts and progresses radiologically in two types of press-fit radial head arthroplasties (RHAs), and to investigate its clinical relevance. Methods. A total of 97 patients with RHA were analyzed: 56 received a bipolar RHA (Group 1) while 41 received an anatomical implant (Group 2). Radiographs were performed postoperatively and after three, six, nine, and 12 weeks, six, nine, 12, 18, and 24 months, and annually thereafter. PRNR was measured in all radiographs in the four radial neck quadrants. The Mayo Elbow Performance Score (MEPS), the abbreviated version of the Disabilities of the Arm, Shoulder, and Hand questionnaire (QuickDASH), and the patient-assessed American Shoulder and Elbow Surgeons score - Elbow (pASES-E) were used for the clinical assessment. Radiological signs of implant loosening were investigated. Results. The mean follow-up was six years (2 to 14). PRNR started after a mean of 7.5 weeks (SD 2.1) and progressed significantly during the first two years, by the end of which the bone resorption stabilized. PRNR was detected in 81% (n = 45) of patients in Group 1 and 88% (n = 36) in Group 2. The final mean PRNR was 3.0 mm (SD 2.3) in Group 1 and 3.7 mm (SD 2.5) in Group 2. The mean MEPS, QuickDASH, and pASES-E were 95.9 (SD 11.5), 4.4 (SD 9.2), and 94.8 (SD 10.9) in Group 1 and 92.2 (SD 16.2), 9.9 (SD 21.5), and 90.8 (SD 15) in Group 2, respectively. No significant differences were observed between groups in the clinical and radiological outcomes. No correlations were found between PRNR and the clinical results. Conclusion. PRNR after press-fit RHA is a common radiological finding that develops in the first 24 months before stabilizing definitively. PRNR does not affect the clinical results or implant survival in the mid term. Cite this article: Bone Joint J 2023;105-B(8):905–911

Aims. Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture. Methods. A total of 102 participants aged 18 to 50 years (median 28 years (interquartile range 23 to 35)), receiving an intramedullary nail for a tibial or femoral shaft fracture, were enrolled in a randomized controlled trial comparing vitamin D. 3. supplementation to placebo. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and N-terminal propeptide of type I procollagen (P1NP; bone formation marker) were measured at baseline, six weeks, and 12 weeks post-injury. Clinical and radiological fracture healing was assessed at three months. Results. CTX and P1NP concentrations peaked at six weeks in all groups. Elevated six-week CTX and P1NP were associated with radiological healing at 12 weeks post-injury (odds ratio (OR) 10.5; 95% confidence interval 2.71 to 53.5, p = 0.002). We found no association between CTX or P1NP and functional healing. Baseline serum 25(OH)D showed a weak inverse relationship with P1NP (p = 0.036) and CTX (p = 0.221) at 12 weeks, but we observed no association between vitamin D supplementation and either BTM. Conclusion. Given the association between six-week BTM concentrations and three-month radiological fracture healing, CTX and P1NP appear to be potential surrogate markers of fracture healing. Cite this article: Bone Joint Res 2022;11(4):239–250

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions. Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2

Aims. LY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling. Methods. The function of LY3023414 was explored in the context of osteogenesis (bone formation by osteoblasts) and osteoclastogenesis (osteoclast formation and bone resorption). Murine preosteoblast MC3T3-E1 cell line and murine bone marrow-derived macrophage cells (BMMs) were subjected to different treatments. An MTS cell proliferation assay was used to examine the cytotoxicity. Thereafter, different induction conditions were applied, such as MCSF and RANKL for osteoclastogenesis and osteogenic media for osteogenesis. Specific staining, a bone resorption assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were subsequently used to evaluate the effect of LY3023414. Moreover, small interfering RNA (siRNA) was applied to knockdown Akt1 or Akt2 for further validation. Lastly, western blot was used to examine the exact mechanism of action. Results. LY3023414 attenuated PI3K/protein kinase B (Akt)/GSK3-dependent activation of β-catenin and nuclear factor-activated T cell 1 (NFATc1) during osteogenesis and osteoclastogenesis, respectively. LY3023414 mainly inhibited osteoclast formation instead of mature osteoclast function. Moreover, it suppressed osteogenesis both in the early stage of differentiation and late stage of calcification. Similarly, gene knockdown of Akt isoforms by siRNA downregulated osteogenic and osteoclastogenic processes, indicating that Akt1 and Akt2 acted synergistically. Conclusion. LY3023414 can suppress osteogenesis and osteoclastogenesis through inhibition of the PI3K/Akt/GSK3 signalling pathway, which highlights the potential benefits and side effects of LY3023414 for future clinical applications. Cite this article: Bone Joint Res 2021;10(4):237–249

Aims. Osteopetrosis (OP) is a rare hereditary disease that causes reduced bone resorption and increased bone density as a result of osteoclastic function defect. Our aim is to review the difficulties, mid-term follow-up results, and literature encountered during the treatment of OP. Methods. This is a retrospective and observational study containing data from nine patients with a mean age of 14.1 years (9 to 25; three female, six male) with OP who were treated in our hospital between April 2008 and October 2018 with 20 surgical procedures due to 17 different fractures. Patient data included age, sex, operating time, length of stay, genetic type of the disease, previous surgery, fractures, complications, and comorbidity. Results. The mean follow-up period was 92.5 months (25 to 140). Bony union was observed in all of our patients. Osteomyelitis developed in two patients with femoral shaft fractures, and two patients had peri-implant stress fractures. Conclusion. Treatment of fractures in OP patients is difficult, healing is protracted, and the risk of postoperative infection is high. In children and young adults with OP who have open medullary canal and the epiphyses are not closed, fractures can be treated with surgical techniques such as intramedullary titanium elastic nail (TENS) technique or fixation with Kirschner (K)-wire. Cite this article: Bone Joint J 2020;102-B(8):1082–1087

Charcot neuroarthropathy is a rare but serious complication of diabetes, causing progressive destruction of the bones and joints of the foot leading to deformity, altered biomechanics and an increased risk of ulceration. Management is complicated by a lack of consensus on diagnostic criteria and an incomplete understanding of the pathogenesis. In this review, we consider recent insights into the development of Charcot neuroarthropathy. It is likely to be dependent on several interrelated factors which may include a genetic pre-disposition in combination with diabetic neuropathy. This leads to decreased neuropeptides (nitric oxide and calcitonin gene-related peptide), which may affect the normal coupling of bone formation and resorption, and increased levels of Receptor activator of nuclear factor kappa-B ligand, potentiating osteoclastogenesis. Repetitive unrecognized trauma due to neuropathy increases levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumour necrosis factor α) which could also contribute to increased bone resorption, in combination with a pre-inflammatory state, with increased autoimmune reactivity and a profile of monocytes primed to transform into osteoclasts - cluster of differentiation 14 (CD14). Increased blood glucose and loss of circulating Receptor for Advanced Glycation End-Products (AGLEPs), leading to increased non-enzymatic glycation of collagen and accumulation of AGLEPs in the tissues of the foot, may also contribute to the pathological process. An understanding of the relative contributions of each of these mechanisms and a final common pathway for the development of Charcot neuroarthropathy are still lacking. Cite this article: S. E. Johnson-Lynn, A. W. McCaskie, A. P. Coll, A. H. N. Robinson. Neuroarthropathy in diabetes: pathogenesis of Charcot arthropathy. Bone Joint Res 2018;7:373–378. DOI: 10.1302/2046-3758.75.BJR-2017-0334.R1

Aims. Limb salvage in bone tumour patients replaces the bone with massive segmental prostheses where achieving bone integration at the shoulder of the implant through extracortical bone growth has been shown to prevent loosening. This study investigates the effect of multidrug chemotherapy on extracortical bone growth and early radiological signs of aseptic loosening in patients with massive distal femoral prostheses. Methods. A retrospective radiological analysis was performed on adult patients with distal femoral arthroplasties. In all, 16 patients were included in the chemotherapy group with 18 patients in the non-chemotherapy control group. Annual radiographs were analyzed for three years postoperatively. Dimensions of the bony pedicle, osseointegration of the hydroxyapatite (HA) collar surface, bone resorption at the implant shoulder, and radiolucent line (RLL) formation around the cemented component were analyzed. Results. A greater RLL score (p = 0.041) was observed at three years postoperatively, with those receiving chemotherapy showing greater radiological loosening compared with those not receiving chemotherapy. Chemotherapy patients experience osteolysis at the shoulder of the ingrowth collar over time (p < 0.001) compared with non-chemotherapy patients where osteolysis was not observed. A greater median percentage integration of the collar surface was observed in the non-chemotherapy group (8.6%, interquartile range (IQR) 0.0% to 37.9%; p = 0.021) at three years. Bone growth around the collar was observed in both groups, and no statistical difference in amount of extracortical bony bridging was seen. Conclusion. Multidrug chemotherapy affects the osseointegration of ingrowth collars and accelerates signs of radiological loosening. This may increase the risk of aseptic loosening in patients with massive segmental implants used to treat bone cancer. Cite this article: Bone Joint Res 2020;9(7):333–340

Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes – the main cellular components in BMAC – interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes.

Cite this article: Bone Joint Res 2024;13(9):462–473.

Aims

Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis.

Aims

Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders.

Aims

This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.

1. In growing rats oestrogen, cortisone and thyroxine in high doses suppress bone formation, and this effect is probably part of a general suppression of body growth. 2. Growth hormone and thyroxine in small doses stimulate both body growth and bone formation. 3. Testosterone has no effect on bone formation. 4. Oestrogen and cortisone suppress bone resorption. The effect of cortisone may be modified in conditions of calcium depletion. 5. Thyroxine appears on the other hand to increase bone resorption. 6. Testosterone has no effect on bone resorption

Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Aims

This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously.

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.

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.

Aims

Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD.

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.

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To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism.

Ununited fractures of the scaphoid with extensive bone resorption are usually treated by bone grafting and internal fixation, using either an open or a minimally invasive technique. We studied the feasibility of percutaneous fixation without bone grafting in a consecutive series of 27 patients with established nonunion of an undisplaced fracture of the scaphoid and extensive local resorption of bone. They were treated by a single surgeon with rigid fixation alone, using a headless cannulated screw inserted through a volar percutaneous technique. Clinical examination, standard radiographs and CT confirmed that the fracture had united in all patients at a mean of 11.6 weeks (8 to 16), and that their functional scores had improved. We concluded that extensive resorption at the fracture site is not an absolute indication for bone grafting, and that percutaneous fixation alone will eventually produce healing of ununited undisplaced fractures of the scaphoid regardless of the size of the gap

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Loosening of components after total knee arthroplasty (TKA) can be associated with the development of radiolucent lines (RLLs). The aim of this study was to assess the rate of formation of RLLs in the cemented original design of the ATTUNE TKA and their relationship to loosening.

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This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night.

Rheumatoid arthritis (RA) is an autoimmune disease that involves T and B cells and their reciprocal immune interactions with proinflammatory cytokines. T cells, an essential part of the immune system, play an important role in RA. T helper 1 (Th1) cells induce interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), and interleukin (IL)-2, which are proinflammatory cytokines, leading to cartilage destruction and bone erosion. Th2 cells primarily secrete IL-4, IL-5, and IL-13, which exert anti-inflammatory and anti-osteoclastogenic effects in inflammatory arthritis models. IL-22 secreted by Th17 cells promotes the proliferation of synovial fibroblasts through induction of the chemokine C-C chemokine ligand 2 (CCL2). T follicular helper (Tfh) cells produce IL-21, which is key for B cell stimulation by the C-X-C chemokine receptor 5 (CXCR5) and coexpression with programmed cell death-1 (PD-1) and/or inducible T cell costimulator (ICOS). PD-1 inhibits T cell proliferation and cytokine production. In addition, there are many immunomodulatory agents that promote or inhibit the immunomodulatory role of T helper cells in RA to alleviate disease progression. These findings help to elucidate the aetiology and treatment of RA and point us toward the next steps.

Cite this article: Bone Joint Res 2022;11(7):426–438.

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 aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model.

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The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG.

Aims

Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy.

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This study aimed to identify the effect of anatomical tibial component (ATC) design on load distribution in the periprosthetic tibial bone of Koreans using finite element analysis (FEA).

The effects of the method of fixation and interface conditions on the biomechanics of the femoral component of the Birmingham hip resurfacing arthroplasty were examined using a highly detailed three-dimensional computer model of the hip. Stresses and strains in the proximal femur were compared for the natural femur and for the femur resurfaced with the Birmingham hip resurfacing. A comparison of cemented versus uncemented fixation showed no advantage of either with regard to bone loading. When the Birmingham hip resurfacing femoral component was fixed to bone, proximal femoral stresses and strains were non-physiological. Bone resorption was predicted in the inferomedial and superolateral bone within the Birmingham hip resurfacing shell. Resorption was limited to the superolateral region when the stem was not fixed. The increased bone strain observed adjacent to the distal stem should stimulate an increase in bone density at that location. The remodelling of bone seen during revision of failed Birmingham hip resurfacing implants appears to be consistent with the predictions of our finite element analysis

Aims

Although the Fitmore Hip Stem has been on the market for almost 15 years, it is still not well documented in randomized controlled trials. This study compares the Fitmore stem with the CementLeSs (CLS) in several different clinical and radiological aspects. The hypothesis is that there will be no difference in outcome between stems.