Osteoarthritis (OA) is a highly prevalent and disabling disease with an unmet therapeutic need. The characteristic cartilage loss and alteration of other joint structures result from a complex interaction of multiple risk factors, with mechanical overload consistently playing a central role. This overload generates an inflammatory response in the cartilage due to the activation of the innate immune response in chondrocytes, which occurs through various cellular mechanisms. Moreover, risk factors associated with obesity, being overweight, and metabolic syndrome enhance the inflammatory response both locally and systemically. OA chondrocytes, the only cells present in articular cartilage, are therefore inflamed and initiate an anabolic process in an attempt to repair the damaged tissue, which ultimately results in an aberrant and dysfunctional process. Under these circumstances, where the cartilage continues to be subjected to chronic mechanical stress, proposing a treatment that stimulates the chondrocytes’ anabolic response to restore tissue structure does not appear to be a therapeutic target with a high likelihood of success. In fact, anabolic drugs proposed for the treatment of OA have yet to demonstrate efficacy. By contrast, multiple therapeutic strategies focused on pharmacologically managing the inflammatory component, both at the joint and systemic levels, have shown promise. Therefore, prioritizing the control of chronic innate pro-inflammatory pathways presents the most viable and promising therapeutic strategy for the effective management of OA. As research continues, this approach may offer the best opportunity to alleviate the burden of this incapacitating disease.

Cite this article: Bone Joint Res 2025;14(3):199–207.

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.

The August 2023 Wrist & Hand Roundup360 looks at: Complications and patient-reported outcomes after trapeziectomy with a Weilby sling: a cohort study; Swelling, stiffness, and dysfunction following proximal interphalangeal joint sprains; Utility of preoperative MRI for assessing proximal fragment vascularity in scaphoid nonunion; Complications and outcomes of operative treatment for acute perilunate injuries: a systematic review; The position of the median nerve in relation to the palmaris longus tendon at the wrist: a study of 784 MR images; Basal fractures of the ulnar styloid? A randomized controlled trial; Proximal row carpectomy versus four-corner arthrodesis in SLAC and SNAC wrist; Managing cold intolerance after hand injury: a systematic review.

Aims

This study investigated the effects of transcatheter arterial embolization (TAE) on pain, function, and quality of life in people with early-stage symptomatic knee osteoarthritis (OA) compared to a sham procedure.

Aims

Osteoporosis can determine surgical strategy for total hip arthroplasty (THA), and perioperative fracture risk. The aims of this study were to use hip CT to measure femoral bone mineral density (BMD) using CT X-ray absorptiometry (CTXA), determine if systematic evaluation of preoperative femoral BMD with CTXA would improve identification of osteopenia and osteoporosis compared with available preoperative dual-energy X-ray absorptiometry (DXA) analysis, and determine if improved recognition of low BMD would affect the use of cemented stem fixation.

Aims

To identify the incidence and risk factors for five-year same-site recurrent disc herniation (sRDH) after primary single-level lumbar discectomy. Secondary outcome was the incidence and risk factors for five-year sRDH reoperation.

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.

Aims

To assess the safety of tranexamic acid (TXA) in a large cohort of patients aged over 65 years who have sustained a hip fracture, with a focus on transfusion rates, mortality, and thromboembolic events.

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The aim of this study is to evaluate the clinical results of operative intervention for femoral metastases which were selected based on expected survival and to discuss appropriate surgical strategies.

Aims

To compare complication-related reoperation rates following primary arthroplasty for proximal humerus fractures (PHFs) versus secondary arthroplasty for failed open reduction and internal fixation (ORIF).

Introduction. Analgesic drugs are often prescribed to patients with low back pain (LBP). Recommendations for non-invasive pharmacological management of LBP from recent clinical practice guidelines were compared with each other and with the best available evidence on drug efficacy. Methods. Guideline recommendations concerning opioids, non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, antidepressants, anticonvulsants and muscle relaxants from national primary care guidelines published within the last 3 years were included in this review. For each pharmacotherapy, the most recent systematic review was included as the best available evidence on drug efficacy and common adverse effects were summarized. Results. Eight recent national clinical practice guidelines were included in this review (from Australia, Belgium, Canada, Denmark, The Netherlands, UK and US). Guidelines are universally moving away from pharmacotherapy due to the limited efficacy and the risk of adverse effects. NSAIDs have replaced paracetamol as the first choice analgesics for LBP in many guidelines. Opioids are considered to be a last resort in all guidelines, but prescriptions of these medications have been increasing over recent years. Only limited evidence exists for the efficacy of antidepressants and anticonvulsants in chronic LBP. Muscle relaxants are one of the analgesics of first choice in the US, but aren't widely available and thus not widely recommended in most other countries. Conclusions. Upcoming guideline updates should shift their focus from pain to function and from pharmacotherapy to non-pharmacologic treatment options. No conflicts of interest. Sources of funding: This review has been supported by a program grant of the Dutch Arthritis Foundation

Background

Polypharmacy of elderly trauma patients entails further difficulties in addition to the fracture treatment. Impaired renal function, altered metabolism and drugs that are potentially delirious or inhibit ossification, are only a few examples which must be carefully considered for the medication in elderly patients. The aim of this study was to investigate, if medication errors could be prevented by orthogeriatric comanagement compared to conventional trauma treatment.

Objectives

We performed a systematic review of the literature to determine the safety and efficacy of bone morphogenetic protein (BMP) compared with bone graft when used specifically for revision spinal fusion surgery secondary to pseudarthrosis.

Introduction. Recent UK national guidelines advocate using a combination of mechanical and pharmacological VTE prophylaxis in patients undergoing lower limb arthroplasty but do not recommend one particular pharmacotherapy over another. Objectives. We compared the results from our two series of patients: one treated with clexane and the other treated with rivaroxaban, with respect to average length of stay, postoperative wound leakage, readmission within 30 days of surgery and re-do surgery. Methods. Both groups were comparable in terms of age, sex and proportion of hip and knee patients. Both groups received mechanical prophylaxis. In the first group 89 patients were given 40 mg subcutaneous clexane once daily from the day prior to surgery until they were independently mobile. The second group comprised 99 patients who were given 10 mg of oral rivaroxaban. The first dose was administered 8–10 hours postoperatively and continued once daily for 14 days for total knee replacement and 35 days for total hip replacement. Results. The mean length of stay was 5 days in the clexane group and 5.5 days in the rivaroxaban group. 24 patients stayed in hospital for 5 days or more because of wound leakage in the rivaroxaban group compared to 10 in the clexane group. 5 patients were readmitted in the clexane group: 3 for pulmonary embolism (PE), 1 for dislocation and 1 for periprosthetic fracture. 5 patients were also readmitted from the rivaroxaban group: 4 for infection and 1 for PE. No patients in the clexane group required re-do surgery. 2 patients in the rivaroxaban group went back to theatre: 1 for haematoma evacuation and 1 for haematoma evacuation and subsequent revision knee arthroplasty. Conclusion. This study raises concern regarding the rates of postoperative complications with rivaroxaban prophylaxis

Calcium and vitamin D are both of key importance for bone health, and their effects on bone appear to begin even in utero and continue throughout life. The dietary requirements for both calcium and vitamin D are different at different stages of the lifespan. Importantly, in Australia the bulk of vitamin D comes from manufacture of vitamin D in the skin from ultraviolet light exposure i.e. from sun exposure, as the amount of vitamin D in foods is low. Vitamin D deficiency is common at all stages of life and some groups are at particularly high risk. Adequate calcium intake and maintaining adequate vitamin D levels are important in childhood for maximising peak bone mass, but the effect of calcium supplementation on bone mineral density is small. The role of vitamin D supplementation in childhood outside of treating rickets is unclear, though there is potential for a clinically significant effect. Calcium and vitamin D supplements have been investigated for the primary prevention of osteoporotic fracture in the elderly. Calcium and vitamin D is effective at reducing non-vertebral and vertebral fractures in the institutionalised elderly but community-based studies show conflicting results. There is no evidence that calcium, vitamin D or the combination of calcium and vitamin D alone prevent fractures in those who have already sustained a low trauma fracture (secondary prevention) but calcium and vitamin D are both important adjunctive treatments in established osteoporosis i.e. in combination with other pharmacotherapies

Considerable numbers of authors have reported the change in periprothetic bone mineral density (BMD) after hip arthroplasty. However, there have been few reports concerning the BMD in the lumbar vertebra, especially for dysplastic hips. Since 1998, we have been measuring the BMD mineral density for 2016 patients by DXA (Dual-energy X-Ray Absorptionmetry method). Among them, we evaluated the BMD in 66 postmenopausal patients with the single side primary arthroplasty, with five years or more follow-up, and also aged 60 or more. We used a DXA densitometer (DPX-IQ, GE Healthcare, Madison, WI, USA). The diagnosis at the surgery was dysplastic osteoarthritis in all patients. The average age at the surgery was 66 (60–81). All patients were female. No patients had the systematic diseases which contributed to the secondary osteoporosis. No patients had received the pharmacotherapy for osteoporosis in the whole therapeutic process. The bed rest was seven from two days after the surgery (different by the operation date). The average follow-up was 7.0 (five to ten) years. The average BMD in the lumbar vertebra before the surgery was 0.996 (0.612 to 1.712) g/cm2. The BMD was 0.971 (0.637 to 1.402) at six month postoperatively, 0.972 (0.552 to 1.740) at one year, 1.004 (0.573 to 1.733) at two years, 1.032 (0.633 to 1.670) at three years, 1.035(0.724 to 1.688) at four years, 1.031 (0.564 to 1.679) at five years, 1.027 (0.734 to 1.647) at six years, 1.042 (0.589 to 1.389) at seven years. At the final follow-up, the BMD was 1.054 (0.589 to 1.647). In 53 patients (80%), the density at the final follow-up increased in comparison to that before the surgery. In 27 patients (41%), the density once decreased six month postoperatively. The density increased at 3 years (t=−1.919, p=0.030), four years (t=−2.523, p=0.015), five years (t=−2.381, p=0.021), seven years (t=−2.822, p=0,007), and at the final-follow-up (−4.076, p= 0.000) in comparison to that before the surgery. The activity of the patients was evaluated by the hip score. The average score was 54.5 (21 to 76) before the surgery. The average score was 88.0 (66 to 100) and increased at the final follow-up in comparison to that before the surgery (t=−13.04, p 0.000). Some authors (eg. Bergström I, 2008, Espar I, 2008, etc.) have pointed out that the appropriate activity may increase the bone density. Presumed from the literatures, the increase of activity after the arthroplasty may have increased the BMD, though the direct correlation was not obvious between the BMD and the amount of hip score (at the final follow-up: r=0.005, p=0.972) in this study

Introduction: Spinal deformities and scoliosis in particular, represent the most prevalent type of orthopaedic deformities in children and adolescents. At present, the most significant problem for clinicians is that there is no proven method or test available to identify children or adolescents at risk of developing AIS or to identify which of the affected individuals are at risk of progression. As a consequence, the application of current treatments, such as bracing or surgical correction, has to be delayed until a significant deformity is detected or until a significant progression is clearly demonstrated, resulting in a delayed and less optimal treatment. Among patients with AIS needing treatment, 80% to 90% will be treated by brace and 10% will need surgery to correct the deformity by spinal instrumentation and fusion of the thoracic and/or lumbar spine. About 15000 such surgeries are done every year in North America, resulting in significant psychological and physical morbidity. Moreover, there is no pharmacotherapy available to either prevent or reduce spinal deformities due mainly to our limited knowledge of AIS aetiopathogenesis. We have recently reconciled the role of melatonin in AIS aetiopathogenesis by demonstrating a melatonin signalling dysfunction occurring in a cell autonomous manner in cells derived from AIS patients exhibiting severe scoliotic deformities. This defect could potentially explain the majority of abnormalities reported in AIS since melatonin receptors and signalling activities are normally found in all tissues and systems affected in AIS, thus offering a very innovative and unifying concept to explain the aetiology of AIS. Moreover, several lines of evidence suggested that inactivation of Gi proteins by an increased phosphorylation of serine residues could be at the source of this signalling defect in AIS. The goals of that study were to assess the possibility to establish a molecular classification of AIS patients and to demonstrate the feasibility to correct this melatonin signalling defect in cells of AIS patients using therapeutic compounds. Methods: Primary cell cultures were prepared from musculoskeletal tissues of AIS patients (n=150) and age- and gender-matched controls (n=35) obtained intra-operatively. An informed consent was obtained for each subject as approved by our Institutional Ethical Committee. The osteoblasts, the bone-forming cells, were selected to assess whether or not an alteration of melatonin signalling pathway occurs in AIS and accordingly to identify which component of the melatonin transduction machinery could be involved. Co-immunoprecipitation experiments with membrane extracts were performed to identify interacting molecules with key components of melatonin signal transduction machinery. The functionality of melatonin signalling was assessed by investigating the ability of Gi proteins to inhibit stimulated adenyl cyclase activity in osteoblast cultures. Inhibition curves of cAMP production were generated by adding melatonin to the forskolin-containing samples in concentrations ranging from 10-11M to 10-5M in a final volume of 1 ml of _-MEM media containing 0.2% bovine serum albumin (BSA) alone or in presence of 2.5 _M of therapeutic compound A or therapeutic compound B (the nature of both compounds tested cannot be disclosed at this stage). The cAMP content was determined using an enzyme immunoassay kit (Amersham-Pharmacia Biosciences). All assays were performed in duplicate. A non-parametric test, the Wilcoxon matched pairs test was performed to verify the significance between 2 means. Significance was defined as P< 0.05. Results: Osteoblasts from patients with AIS showed a lack or a markedly reduced inhibition of forskolin-stimulated adenyl cyclase activity by melatonin generating three distinct response-curves corresponding to three functional groups. In order to identify candidate genes involved in AIS aetiopathogenesis, we focused our attention on known kinases and phosphatases modulating Gi protein functions and characterised their interacting partners. Interestingly, PKC_ was initially targeted owing to its property to phosphorylate Gi proteins in vitro. Indeed, in normal osteoblast interactions occurring between MT2 melatonin receptor and RACK1 (a cytosolic protein that bind to and stabilises the actives form of PKC and permits its translocation to different sites within the cells) and PKC_ were detected although those interactions among different AIS patients were altered. Interestingly, treatment with compound A or B rescued melatonin signal defect in cells derived from 36% and 47% of AIS patients respectively. Overall, melatonin signal transduction was restored in cells of 64% of AIS patients (23/36) when treated by one of these therapeutic compounds. Conclusions: The functional classification of AIS patients is correlated at the molecular level by distinct interactions between key molecules normally involved in melatonin signal transduction in spite that these patients exhibited the same curve type (right thoracic, Lenke type 1). Collectively, these data strongly argue that traditional curve pattern classification is not a relevant stratification of AIS patients to identify its genetic causes. Moreover, using that molecular system we have demonstrated also the possibility to identify therapeutic compounds to rescue the melatonin signalling defect observed in AIS without any prior knowledge of mutations in any defective genes causing AIS because we are measuring a function. Research project supported by La Fondation Yves Cotrel de l’Institut de France

Technological advances and shorter rescue times have allowed early and effective resuscitation after trauma and brought attention to the host response to injury. Trauma patients are at risk of progressive organ dysfunction from what appears to be an uncontrolled immune response. The availability of improved techniques of molecular diagnosis has allowed investigation of the role of genetic variations in the inflammatory response to post-traumatic complications and particularly to sepsis. This review examines the current evidence for the genetic predisposition to adverse outcome after trauma. While there is evidence supporting the involvement of different polymorphic variants of genes in determining the post-traumatic course and the development of complications, larger-scale studies are needed to improve the understanding of how genetic variability influences the responses to post-traumatic complications and pharmacotherapy