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

Objectives. Tranexamic acid (TXA) is an antifibrinolytic agent used as a blood-sparing technique in total knee arthroplasty (TKA), and is routinely administered by intravenous (IV) or intra-articular (IA) injection. Recently, a novel method of TXA administration, the combined IV and IA application of TXA, has been applied in TKA. However, the scientific evidence of combined administration of TXA in TKA is still meagre. This meta-analysis aimed to investigate the efficacy and safety of combined IV and IA TXA in patients undergoing TKA. Materials and Methods. A systematic search was carried out in PubMed, the Cochrane Clinical Trial Register (Issue12 2015), Embase, Web of Science and the Chinese Biomedical Database. Only randomised controlled trials (RCT) evaluating the efficacy and safety of combined use TXA in TKA were identified. Two authors independently identified the eligible studies, extracted data and assessed the methodological quality of included studies. Meta-analysis was conducted using Review Manager 5.3 software. Results. A total of ten RCTs (1143 patients) were included in this study. All the included studies were randomised and the quality of included studies still needed improvement. The results indicated that, compared with either placebo or the single-dose TXA (IV or IA) group, the combination of IV and IA TXA group had significantly less total blood loss, hidden blood loss, total drain output, a lower transfusion rate and a lower drop in haemoglobin level. There were no statistically significant differences in complications such as wound infection and deep vein thrombosis between the combination group and the placebo or single-dose TXA group. Conclusions. Compared with placebo or the single-dose TXA, the combined use of IV and IA TXA provided significantly better results with respect to all outcomes related to post-operative blood loss without increasing the risk of thromboembolic complications in TKA. Cite this article: Z. F. Yuan, H. Yin, W. P. Ma, D. L. Xing. The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: combined tranexamic acid for TKA. Bone Joint Res 2016;5:353–361. DOI: 10.1302/2046-3758.58.BJR-2016-0001.R2

Objectives. Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis. Methods. We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value. Results. With respect to preventing new vertebral fractures (NVF), all ten drugs outperformed placebo, and etidronate proved to be the most effective treatment (OR 0.24, 95% CI 0.14 to 0.39). In addition, zoledronic acid and parathyroid hormone ranked higher compared with the other drugs. With respect to preventing clinical vertebral fractures (CVF), zoledronic acid proved to be the most effective drug (OR = 0.25, 95% CI 0.08 to 0.92), with denosumab as a desirable second option (OR = 0.48, 95% CI 0.22 to 0.96), when both were compared with placebo. As for adverse events (AE) and severe adverse events (SAE), no significant difference was observed. According to SUCRA, etidronate ranked first in preventing CVF; parathyroid hormone and zoledronic acid ranked highly in preventing NVF and CVF. Raloxifene was safe with a high rank in preventing AEs and SAEs though performed unsatisfactorily in efficacy. Conclusions. This study suggests that, taking efficacy and safety into account, parathyroid hormone and zoledronic acid had the highest probability of satisfactory performance in preventing osteoporotic fractures. Cite this article: G. Wang, L. Sui, P. Gai, G. Li, X. Qi, X. Jiang. The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment: Which therapies work best? a network meta-analysis. Bone Joint Res 2017;6:452–463. DOI: 10.1302/2046-3758.67.BJR-2016-0292.R1

Objectives. Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA). Methods. OA was surgically induced in the left knee of female mice. Animal groups included age-matched sham control, OA placebo, and OA treated with Salubrinal or Guanabenz. Three weeks after the induction of OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At three and six weeks, the femora and tibiae were isolated and the sagittal sections were stained with Safranin O. Results. Salubrinal suppressed the progression of OA by downregulating p-NFκB p65 and MMP13. Although Guanabenz elevates the phosphorylation level of eIF2α, it did not suppress the progression of OA. Conclusions. Administration of Salubrinal has chondroprotective effects in arthritic joints. Salubrinal can be considered as a potential therapeutic agent for alleviating symptoms of OA. Cite this article: Bone Joint Res 2015;4:84–92

Objective. Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. . Methods. We performed a pilot international multi-centre RCT. We used central randomisation to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. . Results. We screened 96 patients and enrolled 60 participants (44 men and 16 women) across 21 sites from four countries over 24 months (mean 2.13 participants per site per year, standard deviation 2.14). One participant was lost to follow-up and one withdrew consent. Complete data were obtained for 98% of eligible patients at two weeks, 83% at six months, and 73% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. . Conclusions. It is feasible to conduct a definitive multi-centre RCT of post-operative antibiotic regimens in patients with bone sarcomas, but further expansion of our collaborative network will be critical. We have demonstrated an ability to coordinate in multiple countries, enrol participants, maintain protocol adherence, and minimise losses to follow-up. Cite this article: Bone Joint Res;4:154–162

Cite this article: Bone Joint Res 2023;12(10):654–656.

Aims

Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture).

Aims

To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment.

Aims

Rotator cuff muscle atrophy and fatty infiltration affect the clinical outcomes of rotator cuff tear patients. However, there is no effective treatment for fatty infiltration at this time. High-intensity interval training (HIIT) helps to activate beige adipose tissue. The goal of this study was to test the role of HIIT in improving muscle quality in a rotator cuff tear model via the β3 adrenergic receptor (β3AR).

Aims

A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process.

Aims

This study investigated the effects of β-caryophyllene (BCP) on protecting bone from vitamin D deficiency in mice fed on a diet either lacking (D-) or containing (D+) vitamin D.

Aims

The purpose of this study was to examine the efficacy and safety of carbazochrome sodium sulfonate (CSS) combined with tranexamic acid (TXA) on blood loss and inflammatory responses after primary total hip arthroplasty (THA), and to investigate the influence of different administration methods of CSS on perioperative blood loss during THA.

Objectives. Effective analgesia after total knee arthroplasty (TKA) improves patient satisfaction, mobility and expedites discharge. This study assessed whether continuous femoral nerve infusion (CFNI) was superior to a single-shot femoral nerve block in primary TKA surgery completed under subarachnoid blockade including morphine. Methods. We performed an adequately powered, prospective, randomised, placebo-controlled trial comparing CFNI of 0.125% bupivacaine versus normal saline following a single-shot femoral nerve block and subarachnoid anaesthesia with intrathecal morphine for primary TKA. Patients were randomised to either treatment (CFNI 0 ml to 10 ml/h 0.125% bupivacaine) or placebo (CFNI 0 ml to 10 ml/h normal saline). Both groups received a single-shot femoral nerve block (0.25% 20 ml bupivacaine) prior to placement of femoral nerve catheter and subarachnoid anaesthesia with intrathecal morphine. All patients had a standardised analgesic protocol. The primary end point was post-operative visual analogue scale (VAS) pain score over 72 hours post-surgery. Secondary outcomes were morphine equivalent dose, range of movement, side effects, and length of stay. Results. A total of 86 patients were recruited. Treatment and placebo groups were comparable. No significant difference was found in VAS pain scores, total morphine equivalent requirements, side effects, range of movement, motor block, or length of hospital stay. Conclusion. No significant advantage was found for CFNI over a single-shot femoral block and subarachnoid anaesthesia after TKA. Cite this article: Bone Joint Res 2015;4:11–16

Aims

This study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients.

Aims

The purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical and chronic polyarthritis. Fibroblast-like synoviocytes are mainly involved in joint inflammation and cartilage and bone destruction by inflammatory cytokines and matrix-degrading enzymes in RA. Approaches that induce various cellular growth alterations of synoviocytes are considered as potential strategies for treating RA. However, since synoviocytes play a critical role in RA, the mechanism and hyperplastic modulation of synoviocytes and their motility need to be addressed. In this review, we focus on the alteration of synoviocyte signalling and cell fate provided by signalling proteins, various antioxidant molecules, enzymes, compounds, clinical candidates, to understand the pathology of the synoviocytes, and finally to achieve developed therapeutic strategies of RA.

Cite this article: Bone Joint Res 2021;10(4):285–297.

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

Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process.

Aims

We hypothesized that the wide-awake local anaesthesia with no tourniquet (WALANT) technique is cost-effective, easy to use, safe, and reproducible, with a low learning curve towards mastery, having a high patient satisfaction rate. Furthermore, WALANT would be a suitable alternative for the austere and developing nation environments where lack of funds and resources are a common issue.