Aims. We aimed to develop and validate a novel prediction model for osteoporosis based on serotonin, fat-soluble vitamins, and bone turnover markers to improve prediction accuracy of osteoporosis. Methods. Postmenopausal women aged 55 to 65 years were recruited and divided into three groups based on DXA (normal, osteopenia, and osteoporosis). A total of 109 participants were included in this study and split into healthy (39/109, 35.8%), osteopenia (35/109, 32.1%), and osteoporosis groups (35/109, 32.1%). Serum concentrations of serotonin, fat-soluble vitamins, and bone turnover markers of participants were measured. Stepwise discriminant analysis was performed to identify efficient predictors for osteoporosis. The prediction model was developed based on Bayes and Fisher’s discriminant functions, and validated via leave-one-out cross-validation. Normal and empirical volume under the receiver operating characteristic (ROC) surface (VUS) tests were used to evaluate predictive effects of variables in the prediction model. Results. Significant variables including oestrogen (E2), total procollagen type 1 amino-terminal propeptide (TP1NP), parathyroid hormone (PTH), BMI, vitamin K, serotonin, osteocalcin (OSTEOC), vitamin A, and vitamin D3 were used for the development of the prediction model. The training accuracy for normal, osteopenia, and osteoporosis is 74.4% (29/39), 80.0% (28/35), and 85.7% (30/35), respectively, while the total training accuracy is 79.8% (87/109). The internal validation showed excellent performance with 72.5% testing accuracy (72/109). Among these variables, serotonin and vitamin K exert important roles in the prediction of osteoporosis. Conclusion. We successfully developed and validated a novel prediction model for osteoporosis based on serum concentrations of serotonin, fat-soluble vitamins, and bone turnover markers. In addition, interactive communication between serotonin and fat-soluble vitamins was observed to be critical for bone health in this study. Cite this article: Bone Joint Res 2025;14(2):111–123

There has been growing interest in the literature regarding evaluation of functional outcomes in patients undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA) while suffering from depression and using selective serotonin reuptake inhibitors (SSRI). Previous literature has shown that these patients have lower post-operative functional scores compared to those without SSRI use and with multiple musculoskeletal co-morbidities. This might be the result of potentially suboptimal motivation and participation in the post-operative rehabilitation programs. One recent study from a single center has suggested a reduction in adverse events in patients undergoing arthroplasty while on SSRI. The purpose of this study is to evaluate the post operative functional scores of patients on SSRI and compare them with the patients not prescribed SSRIs. A retrospective data analysis was performed on patients who had primary TKA and primary THA between 1st June 2014 and 31st May 2017. The patients into two groups. In the first, patients received SSRI for at least one year before the surgery while in group two, patients did not receive SSRI. Outcome measures included Western Ontario and McMaster university osteoarthritis index (WOMAC) and EQ5D5L scores at pre surgery, three months and 12 months post surgery. Chi-square and t test was used to compare categorical variables and continuous variables respectively. Multivariate linear regression was conducted to compare the change of scores between the two groups and was adjusted for age, gender, and comorbidities. These outcome scores were analyzed separately for TKA and THA. In the TKA group, there were 1,452 patients using SSRI and 15,981 not using SSR. In the THA group there were 851 patients using SSRIs and 10,102 patients without SSRIs. The baseline WOMAC for TKA patients was 45.6 for the controls and 41.8 for those patients on SSRIs (p < 0 .001). The baseline EQ5DL was 0.53 and 0.46 in the same groups (p < 0 .001). The baseline WOMAC for THA patients was 39.1 for the controls and 36.2 for patients using SSRIs (p < 0 .001). The baseline EQ5DL scores were 0.43 and 0.37respectively, again indicating patients on SSRI therapy had lower baseline scores (p < 0 .001). There was improvement in WOMAC and EQ5DL scores in all patient groups at 3 months and 12 months. After adjusting for gender, age, comorbidities and baseline score, THA patients not using SSRI showed a greater improvement in their WOMAC and EQ5DL scores than those prescribed SSRIs, WOMAC (p=0.008), EQ5DL (p=0.001). TKA patients showed a similar outcome but only the EQ5DL was statistically significant, WOMAC (p=0.12), EQ5DL (p=0.036). Our results show that patients on SSRI have lower preoperative WOMAC and EQ5DL scores at baseline when compared to patients not undergoing treatment for depression or anxiety with SSRIs. After arthroplasty, patients using SSRIs show significant improvement at 12 months but the improvement is smaller than the group not using SSRIs

Aims. Trained immunity confers non-specific protection against various types of infectious diseases, including bone and joint infection. Platelets are active participants in the immune response to pathogens and foreign substances, but their role in trained immunity remains elusive. Methods. We first trained the innate immune system of C57BL/6 mice via intravenous injection of two toll-like receptor agonists (zymosan and lipopolysaccharide). Two, four, and eight weeks later, we isolated platelets from immunity-trained and control mice, and then assessed whether immunity training altered platelet releasate. To better understand the role of immunity-trained platelets in bone and joint infection development, we transfused platelets from immunity-trained mice into naïve mice, and then challenged the recipient mice with Staphylococcus aureus or Escherichia coli. Results. After immunity training, the levels of pro-inflammatory cytokines (tumour necrosis factor alpha (TNF-α), interleukin (IL)-17A) and chemokines (CCL5, CXCL4, CXCL5, CXCL7, CXCL12) increased significantly in platelet releasate, while the levels of anti-inflammatory cytokines (IL-4, IL-13) decreased. Other platelet-secreted factors (e.g. platelet-derived growth factor (PDGF)-AA, PDGF-AB, PDGF-BB, cathepsin D, serotonin, and histamine) were statistically indistinguishable between the two groups. Transfusion of platelets from trained mice into naïve mice reduced infection risk and bacterial burden after local or systemic challenge with either S. aureus or E. coli. Conclusion. Immunity training altered platelet releasate by increasing the levels of inflammatory cytokines/chemokines and decreasing the levels of anti-inflammatory cytokines. Transfusion of platelets from immunity-trained mice conferred protection against bone and joint infection, suggesting that alteration of platelet releasate might be an important mechanism underlying trained immunity and may have clinical implications. Cite this article: Bone Joint Res 2022;11(2):73–81

Introduction. Idiopathic scoliosis (IS) has been associated with several genetic loci in varying study populations, reflecting the disorder's genetic complexity. One region of interest is on chromosome 17, flanking regions linked to neurofibromatosis type 1 (NF1). This region is of particular relevance because the most common osseous manifestation in NF1 is scoliosis (10–30% of patients). This alludes to a potential genetic correlation within this region affecting spinal development or stability. The objective of this research is to identify candidate genes within this region that are statistically linked to IS. Methods. An initial population of IS families recruited through approval by the institutional review board (202 families; 1198 individuals) had DNA harvested from blood, and underwent genomic screening, finemapping, and statistical analyses. We identified a specific familial subset: families with males having undergone surgery for scoliosis (17 families, 147 individuals). The initial genome-wide scan indicated that this subset was linked to chromosome 17q.11.2. The most prominent marker, D17s975, (p=0·0003) at 25.12 Mb is adjacent to the NF1 deletional region. We then analysed a custom panel of single-nucleotide polymorphisms (SNPs) extending from 18·30–31·47 Mb for linkage through Taqman SNP assay protocol. With allele specific fluorescent tags, allelic discrimination was done with real-time PCR. Results. Findings show two regions with two or more contiguous SNPs of significance (p<0·05), confirming significant linkage adjacent to the NF1 locus (table). The most significant results lie within the serotonin transporter gene SLC6A4, whose product is a modulator of serotonin (5-HT) activity. Conclusions. IS is a disorder of variable phenotypic expression that has been related to several regions on the genome. Although NF1 has been definitively associated with a region on chromosome 17, the phenotypic expression is not understood at the molecular level. The elucidation of shared genetic variations within this region by two disorders marked by scoliosis has significance for the molecular understanding of the pathogenesis of scoliosis and axial development. The specific gene, SLC6A4, is of particular interest in that as a modulator of serotonin transport, bone mineral content, density, and mechanical strength can be altered. Both NF1 and IS in some patients have been associated with decreased bone mineral density. Future work will focus on replication of these findings and targeted genetic sequencing

There is little doubt that serotonin influences bone biology. Bone loss in elderly patients on long-term selective serotonin receptor inhibitor (SSRI) or tricyclic (TCA) anti-depressant (AD) medication is considered to be secondary to a more sedentary lifestyle. However, a recent report suggested that in mice treated with SSRIs or TCAs the disturbances in normal bone mass was unrelated to the activity levels of the animal (Warden 2010). This could imply that psychoactive agents have a direct effect on normal bone cell metabolism. We have tested this hypothesis in vitro. Two SSRIs (fluoxetine hydrochloride (FLU) and citalopram hydrobromide (CIT)) and two TCAs (amitriptyline hydrochloride (AMI) and clomipramine hydrochloride (CLO)) in various doses at, above and below serum levels in treated patients (0.06μM–10μM) were added to rat osteoblast-like UMR106 cells and the effect on cell proliferation (DNA content per well) and alkaline phosphatase (AlkP) activity (soluble reaction product) assessed. After 72 hours treatment with SSRI or TCA (0.6μM), there was significant reduction in AlkP activity. DNA content was significantly reduced in all cases, except FLU. These data demonstrate a direct effect of ADs on bone cell behaviour

We studied the possible role of melatonin deficiency in experimentally-induced scoliosis. A total of 90 chickens underwent pinealectomy on the third day after hatching: 30 were treated with serotonin, 30 with melatonin and 30 received no therapy (control group). Scoliosis developed in all the control group, in 22 of the serotonin group, and in only 6 of the melatonin group. The six melatonin-treated chickens with scoliosis had less severe spinal deformities than those in the serotonin-treated group. There were lower blood melatonin concentrations in chickens with scoliosis than in those without. Our findings suggest that melatonin deficiency contributes to the aetiology of this experimental scoliosis, probably by interfering with the normally symmetrical growth of the proprioceptive system involving the paraspinal muscles and the spine

We analysed the effects of commonly used medications on human osteoblastic cell activity in vitro, specifically proliferation and tissue mineralisation. A list of medications was retrieved from the records of patients aged > 65 years filed in the database of the largest health maintenance organisation in our country (> two million members). Proliferation and mineralisation assays were performed on the following drugs: rosuvastatin (statin), metformin (antidiabetic), metoprolol (β-blocker), citalopram (selective serotonin reuptake inhibitor [SSRI]), and omeprazole (proton pump inhibitor (PPI)). All tested drugs significantly stimulated DNA synthesis to varying degrees, with rosuvastatin 5 µg/ml being the most effective among them (mean 225% (. sd. 20)), compared with metformin 10 µg/ml (185% (. sd.  10)), metoprolol 0.25 µg/ml (190% (. sd. 20)), citalopram 0.05 µg/ml (150% (. sd. 10)) and omeprazole 0.001 µg/ml (145% (. sd. 5)). Metformin and metoprolol (to a small extent) and rosuvastatin (to a much higher extent) inhibited cell mineralisation (85% (. sd. 5)). Our results indicate the need to evaluate the medications prescribed to patients in terms of their potential action on osteoblasts. Appropriate evaluation and prophylactic treatment (when necessary) might lower the incidence and costs associated with potential medication-induced osteoporosis. Cite this article: Bone Joint J 2013;95-B:1575–80

Aims

Patient dissatisfaction following primary total knee arthroplasty (TKA) with manual jig-based instruments has been reported to be as high as 30%. Robotic-assisted total knee arthroplasty (RA-TKA) has been increasingly used in an effort to improve patient outcomes, however there is a paucity of literature examining patient satisfaction after RA-TKA. This study aims to identify the incidence of patients who were not satisfied following RA-TKA and to determine factors associated with higher levels of dissatisfaction.

Aims

It is common practice for patients to have postoperative blood tests after total joint replacement (TJR). However, there have been significant improvements in perioperative care with arthroplasty surgery, and a drive to reduce the length of stay (LOS) and move towards day-case TJR. We should reconsider whether this intervention is necessary for all patients.

Introduction: Platelets play a central role in hemostasis and healing processes. Upon their activation, platelet alfa-granules release over 30 cytokines including platelet-derived growth factor (PDGF), transforming growth factor-alfa (TGF-alfa), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), epidermal growth factor (EGF) and also active substances like serotonin, catecholamines, von Willebrand factor, proaccelerin, osteonectin and antimicrobial proteins. By concentrating platelets, platelet-rich plasma (PRP) with higher levels of growth factors might be reached, which could stimulate the healing processes. The activator for PRP is a mixture of thrombin and calcium chloride. After connecting these substances platelet-rich gel (PRG) is formed. Aims: In present study, we investigated in vitro antimicrobial activity of PRG after antibiotic administration. Material and Methods: 30 minutes after iv Amoxillin/ clavulanic acid administration 54 ml of whole blood was collected from each of 10 donors. PRPs were prepared with using GPS system from Biomet. In vitro laboratory susceptibility to PRG was determined by the Kirby-Bauer disc diffusion method on Mueller-Hinton agar (Becton Dickinson). Baseline antimicrobial activity was assessed by measuring the zones of inhibition. Agar plates were coated with one of the following strain: Staphylococcus aureus ATCC 43300 (MRSA), Staphylococcus aureus ATCC 25923 (MSSA), Klebsiella pneumoniae ATCC 700603 (ESBL), Escherichia coli ATCC 35218 (ESBL), Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212 and Pseudomonas aeruginosa ATCC 27853. Results: We tested 10 samples of PRG. Zones of inhibition produced by PRG ranged between 6 – 23 mm in diameter. PRG inhibited the growth of Staphylococcus aureus. PG also was active against Escherichia coli, Enterococcus faecalis. No activity against Klebsiella pneumoniae and Pseudomonas aeruginosa was detected. Conclusions: Our previous study showed PRG no activity against Enterococcus faecalis without antibiotic administration. In this investigation we observed PRG strong activity against this bacteria after iv Amoxicillin-clavulanic acid administration. In infections during antibiotic treatment, PRG antimicrobial properties are enhanced by antibiotics that are concentrated in plasma

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.

Aims

Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations.

Aims

Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD.

Osteoporosis (OP) is a chronic metabolic bone disease characterized by the decrease of bone tissue per unit volume under the combined action of genetic and environmental factors, which leads to the decrease of bone strength, makes the bone brittle, and raises the possibility of bone fracture. However, the exact mechanism that determines the progression of OP remains to be underlined. There are hundreds of trillions of symbiotic bacteria living in the human gut, which have a mutually beneficial symbiotic relationship with the human body that helps to maintain human health. With the development of modern high-throughput sequencing (HTS) platforms, there has been growing evidence that the gut microbiome may play an important role in the programming of bone metabolism. In the present review, we discuss the potential mechanisms of the gut microbiome in the development of OP, such as alterations of bone metabolism, bone mineral absorption, and immune regulation. The potential of gut microbiome-targeted strategies in the prevention and treatment of OP was also evaluated.

Cite this article: Bone Joint Res 2020;9(8):524–530.

Aims

Traditionally, acetabular component insertion during total hip arthroplasty (THA) is visually assisted in the posterior approach and fluoroscopically assisted in the anterior approach. The present study examined the accuracy of a new surgeon during anterior (NSA) and posterior (NSP) THA using robotic arm-assisted technology compared to two experienced surgeons using traditional methods.

Aims

Current guidelines recommend surgery within 48 hours among patients presenting with hip fractures; however, optimal surgical timing for patients on oral anticoagulants (OACs) remains unclear. Individual studies are limited by small sample sizes and heterogeneous outcomes. The aim of this study was to conduct a systematic review and meta-analysis to summarize the effect of pre-injury OACs on time-to-surgery (TTS) and all-cause mortality among older adults with hip fracture treated surgically.

Aims

The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone.