Aims. Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods. A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 10. 5. colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. Results. The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log. 10. (95%) and 1.5-log. 10. (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 10. 3. vs 7.0 × 10. 4. ; p = 0.022; 3.6 × 10. 3. vs 1.0 × 10. 5. ; p = 0.007, respectively) at POD 21. There was a significant 1.6-log. 10. (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 10. 0. vs 4.7 × 10. 1. , respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. Conclusion. In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections. Cite this article: Bone Joint J 2024;106-B(6):632–638

Aims. Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro. Methods. MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry. Results. Benzamil suppressed growth of osteosarcoma cells by inducing apoptosis. Benzamil reduced the expression of cell surface integrins α5, αV, and β1 in MG63 cells, while it only reduced the expression of αV in U2OS cells. Benzamil suppressed the phosphorylation and activation of FAK and STAT3. In addition, mitochondrial function and ATP production were compromised by benzamil. The levels of anti-apoptotic proteins XIAP, Bcl-2, and Bcl-xL were reduced by benzamil. Correspondingly, benzamil potentiated cisplatin- and methotrexate-induced apoptosis in osteosarcoma cells. Conclusion. Benzamil exerts anti-osteosarcoma activity by inducing apoptosis. In terms of mechanism, benzamil appears to inhibit integrin/FAK/STAT3 signalling, which triggers mitochondrial dysfunction and ATP depletion. Cite this article: Bone Joint Res 2024;13(4):157–168

Aims. The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold. Methods. Female Sprague Dawley (SD) rats were used to establish a rat model of BCP, and the messenger RNA (mRNA) and protein expression of ionized calcium binding adaptor molecule 1 (IBA1) and cyclin D1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. The proliferation of spinal microglia was detected by immunohistochemistry. The pain behaviour test was assessed by quantification of spontaneous flinches, limb use, and guarding during forced ambulation, mechanical paw withdrawal threshold, and thermal paw withdrawal latency. Results. IBA1 and cyclin D1 in the ipsilateral spinal horn increased in a time-dependent fashion. Spinal microglia proliferated in BCP rats. The microglia inhibitor minocycline attenuated the pain behaviour in BCP rats. The cyclin-dependent kinase inhibitor flavopiridol inhibited the proliferation of spinal microglia, and was associated with an improvement in pain behaviour in BCP rats. Conclusion. Our results revealed that the inhibition of spinal microglial proliferation was associated with a decrease in pain behaviour in a rat model of BCP. Cyclin D1 acts as a key regulator of the proliferation of spinal microglia in a rat model of BCP. Disruption of cyclin D1, the restriction-point control of cell cycle, inhibited the proliferation of microglia and attenuated the pain behaviours in BCP rats. Cyclin D1 and the proliferation of spinal microglia may be potential targets for the clinical treatment of BCP. Cite this article: Bone Joint Res 2022;11(11):803–813

Aims. Calcium sulphate has traditionally been used as a filler of dead space arising during surgery. Various complications have been described following the use of Stimulan bio-absorbable calcium sulphate beads. This study is a prospective observational study to assess the safety profile of these beads when used in revision arthroplasty, comparing the complication rates with those reported in the literature. Methods. A total of 755 patients who underwent 456 revision total knee arthroplasties (TKA) and 299 revision total hip arthroplasties (THA), with a mean follow-up of 35 months (0 to 78) were included in the study. Results. A total of 32 patients (4.2%) had wound drainage, and this was higher with higher bead volumes and in McPherson grade C patients. There was also a significantly higher bead volume in the 41 patients who developed hypercalcaemia, two of which were symptomatic (p < 0.0001). A total of 13 patients (1.7%) had heterotopic ossification (HO). There was no statistically significant relationship between the development of HO and bead volume (p > 0.05). Conclusion. The strength of this study lies in the large number of patients and the detailed data collection, making it the most comprehensive report available in the literature on the use of calcium sulphate-based bone substitutes. Cite this article: R. Kallala, W. Edwin Harris, M. Ibrahim, M. Dipane, E. McPherson. Use of Stimulan absorbable calcium sulphate beads in revision lower limb arthroplasty: Safety profile and complication rates. Bone Joint Res 2018;7:570–579. DOI: 10.1302/2046-3758.710.BJR-2017-0319.R1

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. Methods. The network of AUR was constructed and a potential pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment. Female ovariectomized (OVX) Institute of Cancer Research mice were intraperitoneally injected with 0.01, 0.1, and 1 mM AUR for four weeks. The bone mineral density (BMD) level was measured by dual-energy X-ray absorptiometry. The bone microstructure was determined by histomorphological changes in the femora. In addition, biochemical analysis of the serum and assessment of the messenger RNA (mRNA) levels of osteoclastic markers were performed. Results. In total, 65.93% of the genes of the AUR network matched with osteoporosis-related genes. Osteoclast differentiation was predicted to be a potential pathway of AUR in osteoporosis. Based on the network pharmacology, the BMD and bone mineral content levels were significantly (p < 0.05) increased in the whole body, femur, tibia, and lumbar spine by AUR. AUR normalized the bone microstructure and the serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bALP), osteocalcin, and calcium in comparison with the OVX group. In addition, AUR treatment reduced TRAP-positive osteoclasts and receptor activator of nuclear factor kappa-B ligand (RANKL). +. nuclear factor of activated T cells 1 (NFATc1). +. expression in the femoral body. Moreover, the expressions of initiators for osteoclastic resorption and bone matrix degradation were significantly (p < 0.05) regulated by AUR in the lumbar spine of the osteoporotic mice. Conclusion. AUR ameliorated bone loss by downregulating the RANKL/NFATc1 pathway, resulting in improvement of osteoporosis. In conclusion, AUR might be an ameliorative cure that alleviates bone loss in osteoporosis via inhibition of osteoclastic activity. Cite this article: Bone Joint Res 2022;11(5):304–316

Aims. Bone regeneration during treatment of staphylococcal bone infection is challenging due to the ability of Staphylococcus aureus to invade and persist within osteoblasts. Here, we sought to determine whether the metabolic and extracellular organic matrix formation and mineralization ability of S. aureus-infected human osteoblasts can be restored after rifampicin (RMP) therapy. Methods. The human osteoblast-like Saos-2 cells infected with S. aureus EDCC 5055 strain and treated with 8 µg/ml RMP underwent osteogenic stimulation for up to 21 days. Test groups were Saos-2 cells + S. aureus and Saos-2 cells + S. aureus + 8 µg/ml RMP, and control groups were uninfected untreated Saos-2 cells and uninfected Saos-2 cells + 8 µg/ml RMP. Results. The S. aureus-infected osteoblasts showed a significant number of intracellular bacteria colonies and an unusual higher metabolic activity (p < 0.005) compared to uninfected osteoblasts. Treatment with 8 µg/ml RMP significantly eradicated intracellular bacteria and the metabolic activity was comparable to uninfected groups. The RMP-treated infected osteoblasts revealed a significantly reduced amount of mineralized extracellular matrix (ECM) at seven days osteogenesis relative to uninfected untreated osteoblasts (p = 0.007). Prolonged osteogenesis and RMP treatment at 21 days significantly improved the ECM mineralization level. Ultrastructural images of the mineralized RMP-treated infected osteoblasts revealed viable osteoblasts and densely distributed calcium crystal deposits within the extracellular organic matrix. The expression levels of prominent bone formation genes were comparable to the RMP-treated uninfected osteoblasts. Conclusion. Intracellular S. aureus infection impaired osteoblast metabolism and function. However, treatment with low dosage of RMP eradicated the intracellular S. aureus, enabling extracellular organic matrix formation and mineralization of osteoblasts at later stage. Cite this article: Bone Joint Res 2022;11(5):327–341

Objectives. Bioresorbable orthopaedic devices with calcium phosphate (CaP) fillers are commercially available on the assumption that increased calcium (Ca) locally drives new bone formation, but the clinical benefits are unknown. Electron beam (EB) irradiation of polymer devices has been shown to enhance the release of Ca. The aims of this study were to: 1) establish the biological safety of EB surface-modified bioresorbable devices; 2) test the release kinetics of CaP from a polymer device; and 3) establish any subsequent beneficial effects on bone repair in vivo. Methods. ActivaScrew Interference (Bioretec Ltd, Tampere, Finland) and poly(L-lactide-co-glycolide) (PLGA) orthopaedic screws containing 10 wt% β-tricalcium phosphate (β-TCP) underwent EB treatment. In vitro degradation over 36 weeks was investigated by recording mass loss, pH change, and Ca release. Implant performance was investigated in vivo over 36 weeks using a lapine femoral condyle model. Bone growth and osteoclast activity were assessed by histology and enzyme histochemistry. Results. Calcium release doubled in the EB-treated group before returning to a level seen in untreated samples at 28 weeks. Extensive bone growth was observed around the perimeter of all implant types, along with limited osteoclastic activity. No statistically significant differences between comparative groups was identified. Conclusion. The higher than normal dose of EB used for surface modification did not adversely affect tissue response around implants in vivo. Surprisingly, incorporation of β-TCP and the subsequent accelerated release of Ca had no significant effect on in vivo implant performance, calling into question the clinical evidence base for these commercially available devices. Cite this article: I. Palmer, S. A. Clarke, F. J Buchanan. Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model: An animal study. Bone Joint Res 2019;8:266–274. DOI: 10.1302/2046-3758.86.BJR-2018-0224.R2

Aims. There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO. 4. ) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO. 4. applied locally to treat ODAI. Methods. A total of 30 operations with ceftriaxone-loaded CaSO. 4. had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results. A total of 37 wound fluid concentrations from 16 operations performed in 14 patients were collected. The ceftriaxone concentrations remained approximately within a range of 100 to 200 mg/l up to three weeks. The median concentration was 108.9 mg/l (interquartile range 98.8 to 142.5) within the first ten days. No systemic adverse reactions were observed. Conclusion. Our study highlights new clinical data of locally administered ceftriaxone with CaSO. 4. as carrier material. The near-constant release of ceftriaxone from CaSO. 4. observed in vitro could be confirmed in vivo. The concentrations remained below known local toxicity thresholds. Cite this article: Bone Joint Res 2022;11(11):835–842

Objectives. Bone void fillers are increasingly being used for dead space management in arthroplasty revision surgery. The aim of this study was to investigate the influence of calcium sulphate bone void filler (CS-BVF) on the damage and wear of total knee arthroplasty using experimental wear simulation. Methods. A total of 18 fixed-bearing U2 total knee arthroplasty system implants (United Orthopedic Corp., Hsinchu, Taiwan) were used. Implants challenged with CS-BVF were compared with new implants (negative controls) and those intentionally scratched with a diamond stylus (positive controls) representative of severe surface damage (n = 6 for each experimental group). Three million cycles (MC) of experimental simulation were carried out to simulate a walking gait cycle. Wear of the ultra-high-molecular-weight polyethylene (UHMWPE) tibial inserts was measured gravimetrically, and damage to articulating surfaces was assessed using profilometry. Results. There was no significant difference (p  >  0.05) between the wear rate of implants challenged with CS-BVF (3.3 mm. 3. /MC (95% confidence interval (CI) 1.8 to 4.8)) and the wear rate of those not challenged (2.8 mm. 3. /MC (95% CI 1.3 to 4.3)). However, scratching the cobalt-chrome (CoCr) significantly (p < 0.001) increased the wear rate (20.6 mm. 3. /MC (95% CI 15.5 to 25.7)). The mean surface roughness of implants challenged with CS-BVF was equivalent to negative controls both after damage simulation (p = 0.98) and at the conclusion of the study (p = 0.28). Conclusion. When used close to articulating surfaces, a low-hardness, high-purity CS-BVF had no influence on wear. When trapped between the articulating surfaces of a total knee arthroplasty, CS-BVF did not scratch the surface of CoCr femoral components, nor did it increase the wear of UHMWPE tibial inserts compared with undamaged negative controls. Cite this article: R. M. Cowie, S. S. Aiken, J. J. Cooper, L. M. Jennings. The influence of a calcium sulphate bone void filler on the third-body damage and polyethylene wear of total knee arthroplasty. Bone Joint Res 2019;8:65–72. DOI: 10.1302/2046-3758.82.BJR-2018-0146.R1

Periprosthetic joint infection (PJI) is a devastating complication for patients and results in greatly increased costs of care for both healthcare providers and patients. More than 15 500 revision hip and knee procedures were recorded in England, Wales and Northern Ireland in 2013, with infection accounting for 13% of revision hip and 23% of revision knee procedures. We report our experience of using antibiotic eluting absorbable calcium sulphate beads in 15 patients (eight men and seven women with a mean age of 64.8 years; 41 to 83) as part of a treatment protocol for PJI in revision arthroplasty. . The mean follow-up was 16 months (12 to 22). We report the outcomes and complications, highlighting the risk of hypercalcaemia which occurred in three patients. We recommend that serum levels of calcium be routinely sought following the implantation of absorbable calcium sulphate beads in orthopaedic surgery. Cite this article: Bone Joint J 2015;97-B:1237–41

Objectives. We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. Materials and Methods. We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy. Results. C2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (. sd. ) 0.8) and BMP-7 (50.6 ng/mg, . sd. 2.2). In vitro, this secretome induced differentiation of skeletal muscle cells L6 towards an osteogenic lineage. Conclusion. Extra cellular matrix proteins and growth factors leaking from a bone cavity, along with a ceramic biomaterial, can synergistically enhance the process of ectopic ossification. The overlaying muscle acts as an osteoinductive niche, and provides the required cells for bone formation. Cite this article: D. B. Raina, A. Gupta, M. M. Petersen, W. Hettwer, M. McNally, M. Tägil, M-H. Zheng, A. Kumar, L. Lidgren. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial. Bone Joint Res 2016;5:500–511. DOI: 10.1302/2046-3758.510.BJR-2016-0133.R1

The changes in serum adjusted ionised calcium and parathyroid hormone (PTH) were prospectively studied in 32 patients with isolated tibial fractures, treated conservatively. We measured serum albumin, adjusted total calcium, phosphate, pH, adjusted ionised calcium and PTH at intervals until the fractures had healed. The mean ionised calcium adjusted for pH fell within 24 hours of injury, and then rose to a peak at between four and six weeks. These changes cannot be explained by changes in serum pH or PTH. The restoration of normal ionised calcium levels after fracture coincided with the period when the callus was being calcified. Analysis of the changes in ionised calcium, phosphate and PTH suggests that PTH levels alter in response to changes in ionised calcium levels. PTH is highest immediately after fracture and lowest, often not recordable, at six weeks. The cause of the changes in the ionised calcium level has yet to be elucidated

1. In two dogs, approximately one to two years and three to four months of age, an experimental comparison was made between the calcium accretion rate as defined by the Bauer-Carlsson-Lindquist equation, and the bone formation rate determined by double tetracycline labelling. 2. The overall calcium accretion rate was determined from the specific activity of the blood plasma, and the urinary and faecal excretion of isotope, following an intravenous tracer dose of Ca. 45. A time of five days after injection was used for the calculation of accretion rates, but data for shorter times of calculation are included. 3. Local accretion rates were obtained for different parts of the skeleton by determining the specific activities of bone samples at the end of the experiment. 4. The amount of isotope the uptake of which was not related to new bone formation (the diffuse component) was determined autoradiographically. 5. Local values for appositional growth rate and bone formation rate were obtained, using sections of undecalcified bone specimens, by measuring the linear separation between two tetracycline bone markers and the area of new bone enclosed by them. 6. In the older dog, the measurements for cortical bone showed that the accretion rate was two to three times as great as the bone formation rate: the observed diffuse component was sufficient to account for the greater part of this difference. Measurement of the bone formation rate for cancellous bone presented difficulties, but the approximate values obtained suggested that the accretion rate and the bone formation rate were of about the same order for this tissue. 7. In the younger dog, the bone formation rate could be determined only in cortical bone: at the sites studied, the values for the accretion rate and the bone formation rate did not differ by more than 20 per cent. It is suggested that this is due partly to the low specific activity of the diffuse component in this young animal, and partly to the relatively large amounts of new bone formed during the period of the experiment. 8. Despite the important differences between the rates of calcium accretion and bone formation that were found to exist in regions where there was only a small amount of new bone formation, there was a strong correlation between the two rates. The value of the accretion rate as a parameter of bone metabolism is clear

1. The changes in serum calcium and phosphorus which occurred in forty-one patients with post-menopausal osteoporosis during treatment with stilboestrol were examined. 2. There was a fall of approximately 15 per cent in mean serum phosphorus and of approximately 3 per cent in mean serum calcium. 3. The fall in serum calcium is considered to furnish some evidence against the theory that the primary action of stilboestrol is a reduction in calcium excretion

Aims

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

Aims

We aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism.

Porous blocks of calcium hydroxyapatite ceramic were evaluated as delivery systems for the sustained release of antibiotics. We tested gentamicin sulphate, cefoperazone sodium, and flomoxef sodium in powder form placed in a cylindrical cavity in calcium hydroxyapatite blocks, using in vitro studies of elution and in vivo studies in rats. Gentamicin sulphate gave a maximum concentration within the first week, which gradually decreased but was still effective at 12 weeks, when 70% of the antibiotic had been released. Even at this stage the antibiotic concentration from a 75 mg dose was five times the minimum inhibitory concentration for staphylococci. In the in vivo studies the release of gentamicin sulphate into the normal bone of rats was at similar rates and levels. The bacteriocidal activity of the drugs was not affected by packing into calcium hydroxyapatite ceramic and the blocks were completely biocompatible on histology. This new system overcomes the disadvantages of other drug delivery systems, avoiding thermal damage to the antibiotics and a second operation for the removal of the carrier. Some mechanical strength is provided by the ceramic and healing may be accelerated by bone ingrowth into its micropores

1. Three cases of localised deposition of calcium salts deep to the origin of the common extensors of the forearm with acute symptoms clinically indistinguishable from "tennis elbow" are described. 2. Reports of nine similar cases have been found in the literature. 3. It is suggested that "tennis elbow" is caused by a lesion, probably an adventitial bursa, in the tissue space between the tendon of origin of the forearm extensors and the capsule of the radio-humeral joint; and that it is the sudden precipitation of calcium phosphate at this site which causes the lesion here described. 4. Acute calcification near the elbow joint is compared with the similar calcification which may occur in the insertion of the supraspinatus tendon. 5. Operative treatment is advised

Aims. Calcium sulphate (CaSO. 4. ) is a resorbable material that can be used simultaneously as filler of a dead space and as a carrier for the local application of antibiotics. Our aim was to describe the systemic exposure and the wound fluid concentrations of vancomycin in patients treated with vancomycin-loaded CaSO. 4. as an adjunct to the routine therapy of bone and joint infections. Patients and Methods. A total of 680 post-operative blood and 233 wound fluid samples were available for analysis from 94 implantations performed in 87 patients for various infective indications. Up to 6 g of vancomycin were used. Non-compartmental pharmacokinetic analysis was performed on the data from 37 patients treated for an infection of the hip. Results. The overall systemic exposure remained within a safe range, even in patients with post-operative renal failure, none requiring removal of the pellets. Local concentrations were approximately ten times higher than with polymethylmethacrylate (PMMA) as a carrier, but remained below reported cell toxicity thresholds. Decreasing concentrations in wound fluid were observed over several weeks, but remained above the common minimum inhibitory concentrations for Staphylococcus up to three months post-operatively. . Conclusion. This study provides the first pharmacokinetic description of the local application of vancomycin with CaSO. 4. as a carrier, documenting slow release, systemic safety and a release profile far more interesting than from PMMA. In particular, considering in vitro data, concentrations of vancomycin active against staphylococcal biofilm were seen for several weeks. Cite this article: Bone Joint J 2017;99-B:1537–44

Successful healing of a nine-year tibial nonunion resistant to six previous surgical procedures was achieved by tissue engineering. We used autologous bone marrow stromal cells (BMSCs) expanded to 5 × 10. 6. cells after three weeks’ tissue culture. Calcium sulphate (CaSO. 4. ) in pellet form was combined with these cells at operation. The nonunion was clinically and radiologically healed two months after implantation. This is the description of on healing of a long-standing tibial nonunion by tissue engineering. The successful combination of BMSCs and CaSO. 4. has not to our knowledge been reported in a clinical setting

1. Two cases of deposition of calcium on the outer side of the knee are described. 2. The condition is believed to be uncommon and does not appear to have been described before. 3. One case resolved with conservative treatment, the other after an operation at which the deposit was found in the tendon of popliteus

1. Two cases of deposition of calcium in the medial ligament of the knee are described. Pain was a prominent feature in both. 2. A review of the literature suggests this is an uncommon condition. 3. The condition closely resembles supraspinatus calcification, and the etiology is probably similar. 4. Both cases were treated by operation, with complete relief of symptoms

An injectable material consisting of calcium sulphate mixed with hydroxyapatite was investigated as a possible alternative to autograft in the restoration of bone defects. The material was studied both in vitro in simulated body fluid (SBF) and in vivo when implanted in rat muscles and into the proximal tibiae of rabbits. Variation in the strength and weight of the material during ageing in SBF was measured. Tissue response, material resorption and bone ingrowth were studied in the animal models. A good tissue response was observed in both the rat muscles and rabbit tibiae without inflammatory reactions or the presence of fibrous tissue. Ageing in SBF showed that during the first week carbonated hydroxyapatite precipitated on the surfaces of the material and this may enhance bone ingrowth

We reviewed the results of 51 patients with benign bone tumours treated by curettage and implantation of calcium hydroxyapatite ceramic (CHA). The mean follow-up was 11.4 years (10 to 15.5). Post-operative fractures occurred in two patients and three had local recurrences; three had slightly limited movement of the adjacent joint and one had mild osteoarthritis. There were no allergic or neoplastic complications. In all cases, radiographs showed that the CHA was well incorporated into the host bone. Statistical analysis showed that absorption of the implanted CHA was greater in males (odds ratio, 6.2; 95% CI, 1.6 to 23.7) and younger patients (odds ratio, 0.6 for increase in age of 10 years; 95% CI, 0.91 to 0.99). However, the implanted CHA was not completely absorbed in any patient. We conclude that CHA is a useful and safe bone substitute for the treatment of benign bone tumours

We report 60 benign bone tumours treated by resection and curettage followed by the implantation of calcium hydroxyapatite ceramic (CHA). After follow-up of six to 60 months (average 36), no patient had local recurrence of the tumour or any adverse effects from the implants. In almost all cases radiography showed that the CHA was well-incorporated into the host bone, with new bone formation in and around the CHA. Corrective remodelling of deformed bone and normal fracture healing suggested that there was normal bone turnover in the presence of the CHA. Histology of biopsies from seven patients showed bone ingrowth into the pore structure of CHA in the central zone of some defects by one year after implantation. CHA appears to be a useful substitute for bone graft in the treatment of some benign tumours

We reviewed histologically the incidence and pathogenesis of the deposition of calcium pyrophosphate dihydrate (CPPD) crystals in the pseudocapsule, femoral and acetabular membranes and periprosthetic tissue at revision of 789 cases of failed total hip replacement. In 13, periprosthetic tissues were found to have deposits of CPPD crystals in areas of cartilaginous metaplasia; four also showed evidence of localised deposition of amyloid. None of the patients had a history of chondrocalcinosis in the hip or other joints. Cartilaginous metaplasia and other changes in periprosthetic tissues may predispose to the deposition of CPPD and associated localised amyloid

A total of 63 women who had an operation for a fracture of the hip was randomly allocated to one year of treatment either with anabolic steroids, vitamin D and calcium (anabolic group) or with calcium only (control group). The thigh muscle volume was measured by quantitative CT. The bone mineral density of the hip, femur and tibia was assessed by quantitative CT and dual-energy x-ray absorptiometry and of the heel by quantitative ultrasound. Quantitative CT showed that the anabolic group did not lose muscle volume during the first 12 months whereas the control group did (p< 0.01). There was less bone loss in the proximal tibia in the anabolic group than in the control group. The speed of gait and the Harris hip score were significantly better in the anabolic group after six and 12 months. Anabolic steroids, even in this moderate dose, given in combination with vitamin D and calcium had a beneficial effect on muscle volume, bone mineral density and clinical function in this group of elderly women

Twenty-three of 46 patients, aged 56 to 95 years, with fracture of the femoral neck (FNF) completed the first trial of 10 months treatment with oral sodium fluoride 60 mg and calcium 1800 mg on alternate days and 1 micrograms of vitamin D1 daily. Pre-treatment and post-treatment biopsy specimens and microradiographs of the iliac crest and metacarpal and spinal radiographs were evaluated together with biopsy material from seven untreated age-matched controls with FNF. In 17 patients the treatment improved the amount and quality of trabecular bone. Cortical thickness increased in nine patients and there were no losses of amount or mineralisation. The treatment was well tolerated by most patients and there were no major side-effects or signs of bone demineralisation. The study also revealed an unexpected rapid post-fracture deterioration of bone tissue in untreated FNF patients; thus there is an increased risk of further fractures which calls for the use of an effective treatment to increase bone mass

Aims

Chronic osteomyelitis may recur if dead space management, after excision of infected bone, is inadequate. This study describes the results of a strategy for the management of deep bone infection and evaluates a new antibiotic-loaded biocomposite in the eradication of infection from bone defects.

We report our experience using a biodegradable calcium sulphate antibiotic carrier containing tobramycin in the surgical management of patients with chronic osteomyelitis. The patients were reviewed to determine the rate of recurrent infection, the filling of bony defects, and any problems with wound healing. A total of 193 patients (195 cases) with a mean age of 46.1 years (16.1 to 82.0) underwent surgery. According to the Cierny–Mader classification of osteomyelitis there were 12 type I, 1 type II, 144 type III and 38 type IV cases. The mean follow-up was 3.7 years (1.3 to 7.1) with recurrent infection occurring in 18 cases (9.2%) at a mean of 10.3 months post-operatively (1 to 25.0). After further treatment the infection resolved in 191 cases (97.9%). Prolonged wound ooze (longer than two weeks post-operatively) occurred in 30 cases (15.4%) in which there were no recurrent infection. Radiographic assessment at final follow-up showed no filling of the defect with bone in 67 (36.6%), partial filling in 108 (59.0%) and complete filling in eight (4.4%). A fracture occurred in nine (4.6%) of the treated osteomyelitic segments at a mean of 1.9 years (0.4 to 4.9) after operation.

We conclude that Osteoset T is helpful in the management of patients with chronic osteomyelitis, but the filling of the defect in bone is variable. Prolonged wound ooze is usually self-limiting and not associated with recurrent infection.

Cite this article: Bone Joint J 2014; 96-B:829–36

We investigated whether strontium-enriched calcium phosphate cement (Sr-CPC)-treated soft-tissue tendon graft results in accelerated healing within the bone tunnel in reconstruction of the anterior cruciate ligament (ACL). A total of 30 single-bundle ACL reconstructions using tendo Achillis allograft were performed in 15 rabbits. The graft on the tested limb was treated with Sr-CPC, whereas that on the contralateral limb was untreated and served as a control. At timepoints three, six, nine, 12 and 24 weeks after surgery, three animals were killed for histological examination. At six weeks, the graft–bone interface in the control group was filled in with fibrovascular tissue. However, the gap in the Sr-CPC group had already been completely filled in with new bone, and there was evidence of the early formation of Sharpey fibres. At 24 weeks, remodelling into a normal ACL–bone-like insertion was found in the Sr-CPC group. Coating of Sr-CPC on soft tissue tendon allograft leads to accelerated graft healing within the bone tunnel in a rabbit model of ACL reconstruction using Achilles tendon allograft.

Cite this article: Bone Joint J 2013;95-B:923–8.

A prospective single-cohort study was designed to include 20 patients with enchondromas but was stopped because of poor early results. Four patients with an enchondroma, three in the proximal humerus and one in the distal femur, were treated by curettage and filling of the defect with Norian SRS cement. Clinical and radiological follow-up including CT and MRI was carried out for 18 months. All three patients with lesions in the proximal humerus had severe pain and limited movement of the shoulder. The radiological and CT appearances of the cement were unchanged at follow-up. There were characteristic appearances of synovitis and periosteitis on MRI in two patients. Since the cement induces a soft-tissue reaction the bony cavity should be sealed with the curetted and burred bone after curettage and introduction of Norian cement, especially in sites where a tourniquet cannot be applied.

Aims. Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections. Methods. Between January 2019 and December 2022, 106 patients with bone and joint infections were treated by five surgeons in five hospitals. Surgical debridement and calcium sulphate bead insertion was performed for local elution of antibiotics in high concentration. In all, 100 patients were available for follow-up at regular intervals. Choice of antibiotic was tailor made for each patient in consultation with microbiologist based on the organism grown on culture and the sensitivity. In majority of our cases, we used a combination of vancomycin and culture sensitive heat stable antibiotic after a thorough debridement of the site. Primary wound closure was achieved in 99 patients and a split skin graft closure was done in one patient. Mean follow-up was 20 months (12 to 30). Results. Overall, six out of 106 patients (5.6%) presented with sepsis and poorly controlled comorbid conditions, and died in the hospital within few days of index surgery. Out of the remaining 100 patients, control of infection was achieved in 95 patients (95%). Persistence of infection was noted in five (5%) patients. Out of these 95 patients that had good control of infection, four patients (4.2%) with gap nonunion needed Masquelet procedure to achieve union. Conclusion. Our multicentre experience confirmed that surgical debridement along with calcium sulphate bead insertion was effective in treating bone and joint infections without any side effects and complications. Cite this article: Bone Jt Open 2023;4(7):516–522

Aims. Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up. Methods. A total of 179 patients received preformed calcium sulphate pellets containing 4% tobramycin (Group OT), and 180 patients had an injectable calcium sulphate/nanocrystalline hydroxyapatite ceramic containing gentamicin (Group CG). Outcome measures were infection recurrence, wound leakage, and subsequent fracture involving the treated segment. Bone-void filling was assessed radiologically at a minimum of six months post-surgery. Results. The median follow-up was 4.6 years (interquartile range (IQR) 3.2 to 5.4; range 1.3 to 10.5) in Group OT compared to 4.9 years (IQR 2.1 to 6.0; range 1.0 to 8.3) in Group CG. The groups had similar defect sizes following excision (both mean 10.9 cm. 3. (1 to 30)). Infection recurrence was higher in Group OT (20/179 (11.2%) vs 8/180 (4.4%), p = 0.019) than Group CG, as was early wound leakage (33/179 (18.4%) vs 18/180 (10.0%), p = 0.024) and subsequent fracture (11/179 (6.1%) vs 1.7% (3/180), p = 0.032). Group OT cases had an odds ratio 2.9-times higher of developing any one of these complications, compared to Group CG (95% confidence interval 1.74 to 4.81, p < 0.001). The mean bone-void healing in Group CG was better than in Group OT, in those with ≥ six-month radiological follow-up (73.9% vs 40.0%, p < 0.001). Conclusion. Local antibiotic carrier choice affects outcome in chronic osteomyelitis surgery. A biphasic injectable carrier with a slower dissolution time was associated with better radiological and clinical outcomes compared to a preformed calcium sulphate pellet carrier. Cite this article: Bone Joint Res 2023;12(7):412–422

Aims. There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). Methods. The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. Results. Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. Conclusion. Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections. Cite this article: Bone Joint Res 2022;11(11):787–802

Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI. Cite this article: Bone Joint J 2022;104-B(5):575–580

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. Methods. A total of 40 female mice were assigned to four treatment groups (n = 10/group): D+ diet with propylene glycol control, D+ diet with BCP, D-deficient diet with control, and D-deficient diet with BCP. The D+ diet is a commercial basal diet, while the D-deficient diet contains 0.47% calcium, 0.3% phosphorus, and no vitamin D. All the mice were housed in conditions without ultraviolet light. Bone properties were evaluated by X-ray micro-CT. Serum levels of klotho were measured by enzyme-linked immunosorbent assay. Results. Under these conditions, the D-deficient diet enhanced the length of femur and tibia bones (p < 0.050), and increased bone volume (BV; p < 0.010) and trabecular bone volume fraction (BV/TV; p < 0.010) compared to D+ diet. With a diet containing BCP, the mice exhibited higher BV and bone mineral density (BMD; p < 0.050) than control group. The trabecular and cortical bone were also affected by vitamin D and BCP. In addition, inclusion of dietary BCP improved the serum concentrations of klotho (p < 0.050). In mice, klotho regulates the expression level of cannabinoid type 2 receptor (Cnr2) and fibroblast growth factor 23 (Fgf23) through CD300a. In humans, data suggest that klotho is connected to BMD. The expression of klotho is also associated with bone markers. Conclusion. These data indicate that BCP enhances the serum level of klotho, leading to improved bone properties and mineralization in an experimental mouse model. Cite this article: Bone Joint Res 2022;11(8):528–540

Objectives. This study was conducted to evaluate the cytokine-release kinetics of platelet-rich plasma (PRP) according to different activation protocols. Methods. Two manual preparation procedures (single-spin (SS) at 900 g for five minutes; double-spin (DS) at 900 g for five minutes and then 1500 g for 15 minutes) were performed for each of 14 healthy subjects. Both preparations were tested for platelet activation by one of three activation protocols: no activation, activation with calcium (Ca) only, or calcium with a low dose (50 IU per 1 ml PRP) of thrombin. Each preparation was divided into four aliquots and incubated for one hour, 24 hours, 72 hours, and seven days. The cytokine-release kinetics were evaluated by assessing PDGF, TGF, VEGF, FGF, IL-1, and MMP-9 concentrations with bead-based sandwich immunoassay. Results. The concentration of cytokine released from PRP varied over time and was influenced by various activation protocols. Ca-only activation had a significant effect on the DS PRPs (where the VEGF, FGF, and IL-1 concentrations were sustained) while Ca/thrombin activation had effects on both SS and DS PRPs (where the PDGF and VEGF concentrations were sustained and the TGF and FGF concentrations were short). The IL-1 content showed a significant increase with Ca-only or Ca/thrombin activation while these activations did not increase the MMP-9 concentration. Conclusion. The SS and DS methods differed in their effect on cytokine release, and this effect varied among the cytokines analysed. In addition, low dose of thrombin/calcium activation increased the overall cytokine release of the PRP preparations over seven days, relative to that with a calcium-only supplement or non-activation. Cite this article: Professor J. H. Oh. Cytokine-release kinetics of platelet-rich plasma according to various activation protocols. Bone Joint Res 2016;5:37–45. doi: 10.1302/2046-3758.52.2000540

Total knee arthroplasty (TKA) is known to lead to a reduction in periprosthetic bone mineral density (BMD). In theory, this may lead to migration, instability and aseptic loosening of the prosthetic components. Bisphosphonates inhibit bone resorption and may reduce this loss in BMD. We hypothesised that treatment with bisphosphonates and calcium would lead to improved BMD and clinical outcomes compared with treatment with calcium supplementation alone following TKA. A total of 26 patients, (nine male and 17 female, mean age 67 years) were prospectively randomised into two study groups: alendronate and calcium (bisphosphonate group, n = 14) or calcium only (control group, n = 12). Dual energy X-ray absorptiometry (DEXA) measurements were performed post-operatively, and at three months, six months, one, two, four, and seven years post-operatively. . Mean femoral metaphyseal BMD was significantly higher in the bisphosphonate group compared with controls, up to four years following surgery in some areas of the femur (p = 0.045). BMD was observed to increase in the lateral tibial metaphysis in the bisphosphonate group until seven years (p = 0.002), and was significantly higher than that observed in the control group throughout (p = 0.024). There were no significant differences between the groups in the central femoral metaphyseal, tibial medial metaphyseal or diaphyseal regions of interest (ROI) of either the femur or tibia. Bisphosphonate treatment after TKA may be of benefit for patients with poor bone quality. However, further studies with a larger number of patients are necessary to assess whether this is clinically beneficial. Cite this article: Bone Joint J 2015;97-B:337–45

Aims. The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Methods. Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods. Results. The coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface. Conclusion. In this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection. Cite this article: Bone Joint J 2021;103-B(3):522–529

Aims. Platelet concentrates, like platelet-rich plasma (PRP) and platelet lysate (PL), are widely used in regenerative medicine, especially in bone regeneration. However, the lack of standard procedures and controls leads to high variability in the obtained results, limiting their regular clinical use. Here, we propose the use of platelet-derived extracellular vesicles (EVs) as an off-the-shelf alternative for PRP and PL for bone regeneration. In this article, we evaluate the effect of PL-derived EVs on the biocompatibility and differentiation of mesenchymal stromal cells (MSCs). Methods. EVs were obtained first by ultracentrifugation (UC) and then by size exclusion chromatography (SEC) from non-activated PL. EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and the expression of CD9 and CD63 markers by western blot. The effect of the obtained EVs on osteoinduction was evaluated in vitro on human umbilical cord MSCs by messenger RNA (mRNA) expression analysis of bone markers, alkaline phosphatase activity (ALP), and calcium (Ca. 2+. ) content. Results. Osteogenic differentiation of MSCs was confirmed when treated with UC-isolated EVs. In order to disprove that the effect was due to co-isolated proteins, EVs were isolated by SEC. Purer EVs were obtained and proved to maintain the differentiation effect on MSCs and showed a dose-dependent response. Conclusion. PL-derived EVs present an osteogenic capability comparable to PL treatments, emerging as an alternative able to overcome PL and PRP limitations. Cite this article: Bone Joint Res 2020;9(10):667–674

Aims. Bone health assessment and the prescription of medication for secondary fracture prevention have become an integral part of the acute management of patients with hip fracture. However, there is little evidence regarding compliance with prescription guidelines and subsequent adherence to medication in this patient group. Patients and Methods. The World Hip Trauma Evaluation (WHiTE) is a multicentre, prospective cohort of hip fracture patients in NHS hospitals in England and Wales. Patients aged 60 years and older who received operative treatment for a hip fracture were eligible for inclusion in WHiTE. The prescription of bone protection medications was recorded from participants’ discharge summaries, and participant-reported use of bone protection medications was recorded at 120 days following surgery. Results. Of 5456 recruited patients with baseline data, 2853 patients (52%) were prescribed bone protection medication at discharge, of which oral bisphosphonates were the most common, 4109 patients (75%) were prescribed vitamin D or calcium, and 606 patients (11%) were not prescribed anything. Of those prescribed a bone protection medication, only 932 patients (33%) reported still taking their medication 120 days later. Conclusion. These data provide a reference for current prescription and adherence rates. Adherence with oral medication remains poor in patients with hip fracture. Cite this article: Bone Joint J 2019;101-B:1402–1407

The continual cycle of bone formation and resorption is carried out by osteoblasts, osteocytes, and osteoclasts under the direction of the bone-signaling pathway. In certain situations the host cycle of bone repair is insufficient and requires the assistance of bone grafts and their substitutes. The fundamental properties of a bone graft are osteoconduction, osteoinduction, osteogenesis, and structural support. Options for bone grafting include autogenous and allograft bone and the various isolated or combined substitutes of calcium sulphate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. Not all bone grafts will have the same properties. As a result, understanding the requirements of the clinical situation and specific properties of the various types of bone grafts is necessary to identify the ideal graft. We present a review of the bone repair process and properties of bone grafts and their substitutes to help guide the clinician in the decision making process. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):6–9

Aims. The early mortality in patients with hip fractures from bony metastases is unknown. The objectives of this study were to quantify 30- and 90-day mortality in patients with proximal femoral metastases, and to create a mortality prediction tool based on biomarkers associated with early death. Methods. This was a retrospective cohort study of consecutive patients referred to the orthopaedic department at a UK trauma centre with a proximal femoral metastasis (PFM) over a seven-year period (2010 to 2016). The study group were compared to a matched control group of non-metastatic hip fractures. Minimum follow-up was one year. Results. There was a 90-day mortality of 46% in patients with metastatic hip fractures versus 12% in controls (89/195 and 24/192, respectively; p < 0.001). Mean time to surgery was longer in symptomatic metastases versus complete fractures (9.5 days (SD 19.8) and 3.4 days (SD 11.4), respectively; p < 0.05). Albumin, urea, and corrected calcium were all independent predictors of early mortality and were used to generate a simple tool for predicting 90-day mortality, titled the Metastatic Early Prognostic (MEP) score. An MEP score of 0 was associated with the lowest risk of death at 30 days (14%, 3/21), 90 days (19%, 4/21), and one year (62%, 13/21). MEP scores of 3/4 were associated with the highest risk of death at 30 days (56%, 5/9), 90 days (100%, 9/9), and one year (100%, 9/9). Neither age nor primary cancer diagnosis was an independent predictor of mortality at 30 and 90 days. Conclusion. This score could be used to predict early mortality and guide perioperative counselling. The delay to surgery identifies a potential window to intervene and correct these abnormalities with the aim of improving survival. Cite this article: Bone Joint J. 2020;102-B(1):72–81

Objectives. In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. Methods. We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs. Results. A total of three microarray studies were selected for integrated analysis. In all, 1125 genes were found to be significantly differentially expressed between osteoporosis patients and normal controls, with 373 upregulated and 752 downregulated genes. Positive regulation of the cellular amino metabolic process (gene ontology (GO): 0033240, false discovery rate (FDR) = 1.00E + 00) was significantly enriched under the GO category for biological processes, while for molecular functions, flavin adenine dinucleotide binding (GO: 0050660, FDR = 3.66E-01) and androgen receptor binding (GO: 0050681, FDR = 6.35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). Conclusion. Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and bone formation. Cite this article: J. J. Li, B. Q. Wang, Q. Fei, Y. Yang, D. Li. Identification of candidate genes in osteoporosis by integrated microarray analysis. Bone Joint Res 2016;5:594–601. DOI: 10.1302/2046-3758.512.BJR-2016-0073.R1

Aims. This study is a prospective, non-randomized trial for the treatment of fractures of the medial malleolus using lean, bioabsorbable, rare-earth element (REE)-free, magnesium (Mg)-based biodegradable screws in the adult skeleton. Methods. A total of 20 patients with isolated, bimalleolar, or trimalleolar ankle fractures were recruited between July 2018 and October 2019. Fracture reduction was achieved through bioabsorbable Mg-based screws composed of pure Mg alloyed with zinc (Zn) and calcium (Ca) ( Mg-Zn0.45-Ca0.45, in wt.%; ZX00). Visual analogue scale (VAS) and the presence of complications (adverse events) during follow-up (12 weeks) were used to evaluate the clinical outcomes. The functional outcomes were analyzed through the range of motion (ROM) of the ankle joint and the American Orthopaedic Foot and Ankle Society (AOFAS) score. Fracture reduction and gas formation were assessed using several plane radiographs. Results. The follow-up was performed after at least 12 weeks. The mean difference in ROM of the talocrural joint between the treated and the non-treated sites decreased from 39° (SD 12°) after two weeks to 8° (SD 11°) after 12 weeks (p ≤ 0.05). After 12 weeks, the mean AOFAS score was 92.5 points (SD 4.1). Blood analysis revealed that Mg and Ca were within a physiologically normal range. All ankle fractures were reduced and stabilized sufficiently by two Mg screws. A complete consolidation of all fractures was achieved. No loosening or breakage of screws was observed. Conclusion. This first prospective clinical investigation of fracture reduction and fixation using lean, bioabsorbable, REE-free ZX00 screws showed excellent clinical and functional outcomes. Cite this article: Bone Joint Res 2020;9(8):477–483

Aims. Rheumatoid arthritis (RA) is a systematic autoimmune disorder, characterized by synovial inflammation, bone and cartilage destruction, and disease involvement in multiple organs. Although numerous drugs are employed in RA treatment, some respond little and suffer from severe side effects. This study aimed to screen the candidate therapeutic targets and promising drugs in a novel method. Methods. We developed a module-based and cumulatively scoring approach that is a deeper-layer application of weighted gene co-expression network (WGCNA) and connectivity map (CMap) based on the high-throughput datasets. Results. Four noteworthy RA-related modules were identified, revealing the immune- and infection-related biological processes and pathways involved in RA. HLA-DMA, HLA-DMB, HLA-DPA1, HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DRB1, BLNK, BTK, CD3D, CD4, IL2RG, INPP5D, LCK, PTPRC, RAC2, SYK, and VAV1 were recognized as the key hub genes with high connectivity in gene regulation networks and gene pathway networks. Moreover, the long noncoding RNAs (lncRNAs) in the RA-related modules, such as FAM30A and NEAT1, were identified as the indispensable interactors with the hub genes. Finally, candidate drugs were screened by developing a cumulatively scoring approach based on the selected modules. Niclosamide and the other compounds of T-type calcium channel blocker, IKK inhibitor, and PKC activator, HIF activator, and proteasome inhibitor, which harbour the similar gene signature with niclosamide, were promising drugs with high specificity and broad coverage for the RA-related modules. Conclusion. This study provides not only the promising targets and drugs for RA but also a novel methodological insight into the target and drug screening. Cite this article: Bone Joint Res 2020;9(8):501–514

Aims. Osteoarthritis (OA) is the most prevalent joint disease. However, the specific and definitive genetic mechanisms of OA are still unclear. Methods. Tissue-related transcriptome-wide association studies (TWAS) of hip OA and knee OA were performed utilizing the genome-wide association study (GWAS) data of hip OA and knee OA (including 2,396 hospital-diagnosed hip OA patients versus 9,593 controls, and 4,462 hospital-diagnosed knee OA patients versus 17,885 controls) and gene expression reference to skeletal muscle and blood. The OA-associated genes identified by TWAS were further compared with the differentially expressed genes detected by the messenger RNA (mRNA) expression profiles of hip OA and knee OA. Functional enrichment and annotation analysis of identified genes was performed by the DAVID and FUMAGWAS tools. Results. We detected 33 common genes, eight common gene ontology (GO) terms, and one common pathway for hip OA, such as calcium and integrin-binding protein 1 (CIB1) (PTWAS = 0.025, FCmRNA = -1.575 for skeletal muscle), adrenomedullin (ADM) (PTWAS = 0.022, FCmRNA = -4.644 for blood), Golgi apparatus (PTWAS <0.001, PmRNA = 0.012 for blood), and phosphatidylinositol 3' -kinase-protein kinase B (PI3K-Akt) signalling pathway (PTWAS = 0.033, PmRNA = 0.005 for blood). For knee OA, we detected 24 common genes, eight common GO terms, and two common pathways, such as histocompatibility complex, class II, DR beta 1 (HLA-DRB1) (PTWAS = 0.040, FCmRNA = 4.062 for skeletal muscle), Follistatin-like 1 (FSTL1) (PTWAS = 0.048, FCmRNA = 3.000 for blood), cytoplasm (PTWAS < 0.001, PmRNA = 0.005 for blood), and complement and coagulation cascades (PTWAS = 0.017, PmRNA = 0.001 for skeletal muscle). Conclusion. We identified a group of OA-associated genes and pathways, providing novel clues for understanding the genetic mechanism of OA. Cite this article:Bone Joint Res. 2020;9(3):130–138

The aim of this study was to determine the effectiveness of antibiotic-impregnated implants in the prevention of bone infection. We used a model of contaminated fracture in goats to evaluate four treatment groups: no treatment, hand-made tobramycin-impregnated polymethylmethacrylate beads, commercially-available tobramycin-impregnated calcium sulphate pellets and commercially-available tobramycin-impregnated polymethylmethacrylate beads. Three weeks after intraosseous inoculation with streptomycin-resistant Staphylococcus aureus tissue cultures showed no evidence of infection in any of the antibiotic-treated groups. All of the cultures were positive in the untreated group. These results show that effective local antibiotic delivery can be obtained with both commercially-available products and with hand-made polymethylmethacrylate beads. The calcium sulphate pellets have the advantage of being bioabsorbable, thereby obviating the need for a second procedure to remove them

Objectives. The aim of this study was to analyze drain fluid, blood, and urine simultaneously to follow the long-term release of vancomycin from a biphasic ceramic carrier in major hip surgery. Our hypothesis was that there would be high local vancomycin concentrations during the first week with safe low systemic trough levels and a complete antibiotic release during the first month. Methods. Nine patients (six female, three male; mean age 75.3 years (sd 12.3; 44 to 84)) with trochanteric hip fractures had internal fixations. An injectable ceramic bone substitute, with hydroxyapatite in a calcium sulphate matrix, containing 66 mg of vancomycin per millilitre, was inserted to augment the fixation. The vancomycin elution was followed by simultaneously collecting drain fluid, blood, and urine. Results. The antibiotic concentration in the drain reached a peak during the first six hours post-surgery (mean 966.1 mg/l), which decreased linearly to a mean value of 88.3 mg/l at 2.5 days. In the urine, the vancomycin concentration reached 99.8 mg/l during the first two days, followed by a logarithmic decrease over the next two weeks to reach 0 mg/l at 20 days. The systemic concentration of vancomycin measured in blood serum was low and decreased linearly from 2.17 mg/l at one hour post-surgery to 0 mg/l at four days postoperatively. Conclusion. This is the first long-term pharmacokinetic study that reports vancomycin release from a biphasic injectable ceramic bone substitute. The study shows initial high targeted local vancomycin levels, sustained and complete release at three weeks, and systemic concentrations well below toxic levels. The plain ceramic bone substitute has been proven to regenerate bone but should also be useful in preventing bone infection. Cite this article: M. Stravinskas, M. Nilsson, A. Vitkauskiene, S. Tarasevicius, L. Lidgren. Vancomycin elution from a biphasic ceramic bone substitute. Bone Joint Res 2019;8:49–54. DOI: 10.1302/2046-3758.82.BJR-2018-0174.R2

1. Radiological, chemical and histological examinations have been made of the lumbar vertebral bodies in 100 necropsies on patients dying in a general hospital, with a view to determining the range of variation of calcium content and radiographic density in normal and osteoporotic bone. 2. Radiographs were made of sagittal mid-line vertebral body slabs uniformly one centimetre in thickness, and the radiographic density of these specimens was measured in relation to an aluminium step-wedge of one to ten units. Radio-opacity of different vertebrae ranged from four to ten units. The specimen radiographs also clearly revealed the trabecular structure and the lateral profile of the bones. 3. Calcium was chemically estimated and expressed as weight of the element per unit volume of the whole bone mass (that is, of anatomical bone including soft marrow tissue). It ranged from 38 to 102 milligrams per cubic centimetre of bone. In 75 per cent of the cases the range was 50-84 milligrams per cubic centimetre. High calcium values were mostly encountered in young adults, and the calcium per unit volume tended to diminish with age; but a wide range of calcium was still encountered in the older subjects and a better correlation with age was achieved by radiographic density. Both calcium content and radiographic density tended to be higher in the male than in the female bones at all ages. 4. The results of both calcium and radiographic density showed a smooth distribution curve, though skewed through the inclusion in the series of more older people with less mineralised bones; the absence of a double peak in these curves suggests that the examinations were made on a homogeneous population and does not indicate a separate pathological group of osteoporotic subjects. 5. Arbitrary standards must be used to distinguish osteoporotic from normal bones, since neither radiological measurement or chemical assay, nor histological assessment, reveals a point at which the two groups can be separated. In the present series it seemed to us satisfactory to regard as abnormal all bones showing a radiographic density of five or less step-wedge units, and by this standard nineteen of the 100 cases (eight male, eleven female) were deemed to be osteoporotic. Histological examination excluded other forms of bone rarefaction. 6. The regression of calcium on the density measurements proved to be statistically significant and was not affected either by age or by the number of days in bed during the last illness. A small difference between the sexes was apparent, there being slightly less calcium in female than in male bones of equal radiographic density. Provided this is taken into account, the radiographic density scale can be used to predict the calcium content of vertebral bone specimens and should prove a rapid and accurate method in a survey of osteoporosis in post-mortem room material

1. Individuals who are normal and not osteoporotic seem to show retention of cortical bone at successive decades of life in proportion to the total lean body-mass. In patients with osteoporosis the weight of the skeleton decreases at a rate exceeding the physiological rate of atrophy of muscle, tendon and bone tissue that occurs with the time-dependent process of ageing. 2. Six patients representing the typical forms of osteoporosis commonly found in orthopaedic practice were investigated intensively over a period of three years and compared with individuals in whom there was no osteoporosis by studies of metabolic balance, Sr85 osteograms, and tetracycline deposition. 3. Studies of metabolic balance in patients with osteoporosis showed normal or negative calcium balances, but an equilibrium for the metabolism of nitrogen and phosphorus. Increased intake of calcium in the diet produced retention of calcium but not sufficient phosphorus, nitrogen or gain in weight to prove that the patient had made new bone and healed the osteoporosis. 4. Radio-isotope osteograms showed high, normal or low rates of change of uptake of Sr85 and the accretion rate was calculated to be normal or low in individuals with osteoporosis. High uptake of tetracycline by a small mass of bone tissue and by a relatively small percentage of the total number of osteons suggested that in an adult human being the calcium reserve in the skeleton is enormous. Thirty to 50 per cent of the total bone mass was sufficient to turn over 0·5 to 1·0 gramme, the amount of calcium utilised in twenty-four hours by the human adult. This was accomplished by structural or old bone throughout the entire skeleton, and by labile or newer bone located in approximately 10 per cent of the total number of Haversian cylinders or osteons. 5. Some of the unclosed or half-closed osteons were hyperactive in osteoporotic bones. In the process of remodelling of cortical bone a significant quantity of bone tissue was incompletely restored and there were, presumably as a result, intermittently large or small negative calcium balances. Osteoporosis may have been the cause, rather than the result, of the negative calcium balance. 6. The experimental and clinical literature of the past ten years, and studies on patients described in this critical review, were interpreted to indicate that prolonged calcium deficiency, castration, hyperadrenal corticoidism or a sedentary life may precipitate, accentuate and accelerate osteoporosis in individuals who are genetically predisposed to develop it. Sometimes high calcium intake or sex hormones, or both, may have slowed the rate of resorption but did not replace the deficit in cortical bone. 7. Further research is necessary to find the chief etiological factor and to produce the cure for this increasingly common disorder of the skeleton

Aims. The purpose of this study was to identify prognostic indicators of outcome at presentation to the orthopaedic surgeon, in patients with metastatic prostate cancer. Our aim was to use this information in a pragmatic, clinic-based approach so that surgical decision making could be optimized to benefit the patient in their remaining lifetime. Patients and Methods. A cohort analysis was undertaken of all patients with metastatic disease of the prostate who presented to a regional orthopaedic centre in the United Kingdom between 2003 and 2016. Biochemical data were collected in addition to disease and demographic data. These included: prostate-specific antigen (PSA) at orthopaedic presentation; haemoglobin (Hb); platelets (plt); alkaline phosphatase (ALP); albumin (Alb); and corrected calcium (CaC). Statistical analysis included Kaplan–Meier survival analysis, and a Cox proportional hazards model was fitted to the data. Results. From the departmental database, 137 episodes were identified in 136 patients with a median age at presentation of 72 years (interquartile range (IQR) 66 to 78). Most patients had stage IV disease (n = 98, 72%), and most did not undergo surgical intervention. At one-year follow-up, 50% of patients had died. Biomarkers found to be independently associated with poor survival were: low Hb, low Alb, relatively low PSA (< 30 mmol/l), and a raised ALP. Patients who needed surgical intervention had a poorer survival rate than patients who were managed nonoperatively. Conclusion. The study findings are important for orthopaedic clinical practice in the management of patients with metastatic prostate cancer. The interpretation of routine blood tests can help to predict survival in patients who present with orthopaedic manifestations of prostate cancer. A lower PSA is not necessarily a good prognostic sign. We believe that simple blood testing should be carried out routinely when assessing a patient, guiding potential surgical management and palliative care in the future

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The involvement of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cell (MSC) osteogenic differentiation during osteoporosis (OP) development has attracted much attention. In this study, we aimed to disclose how LINC01089 functions in human mesenchymal stem cell (hMSC) osteogenic differentiation, and to study the mechanism by which LINC01089 regulates MSC osteogenesis.

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Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects.

1. Metabolic balance studies in two cases of the Fanconi syndrome are presented. 2. The actions of sodium bicarbonate and calciferol on the calcium and phosphorus balance were observed separately in the two cases. 3. The results show that sodium bicarbonate alone corrects acidosis and decreases the loss of calcium in the urine. 4. Calciferol in high dosage will increase intestinal absorption of calcium and phosphorus, but the urine calcium excretion then increases and vitamin D alone does not, therefore, give a positive balance adequate for complete healing and normal growth. 5. Alkalies and calciferol together put these cases into strongly positive calcium and phosphorus balance and promote healing of rickets, osteomalacia and pseudo-fractures. 6. Large doses of sodium bicarbonate in tablet form correct acidosis, do not adversely affect intestinal absorption of calcium, and facilitate accurate dosage and convenient administration. 7. Alkali therapy may lower serum potassium and precipitate symptoms of hypokalaemia in potassium-losing patients. This is thought to have been the cause of symptoms in several cases reported in the literature

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.

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Long non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP.

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Astragalus polysaccharide (APS) participates in various processes, such as the enhancement of immunity and inhibition of tumours. APS can affect osteoporosis (OP) by regulating the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). This study was designed to elucidate the mechanism of APS in hBMSC proliferation and osteoblast differentiation.

We undertook a multicentre, prospective study of a series of 112 unstable trochanteric fractures in order to evaluate if internal fixation with a sliding screw device combined with augmentation using a calcium phosphate degradable cement (Norian SRS) could improve the clinical, functional and radiological outcome when compared with fractures treated with a sliding screw device alone. Pain, activities of daily living, health status (SF-36), the strength of the hip abductor muscles and radiological outcome were analysed. Six weeks after surgery, the patients in the augmented group had significantly lower global and functional pain scores (p < 0.003), less pain after walking 50 feet (p < 0.01), and a better return to the activities of daily living (p < 0.05). At follow-up at six weeks and six months, those in the augmented group showed a significant improvement compared with the control group in the SF-36 score. No other significant differences were found between the groups. We conclude that augmentation with calcium phosphate cement in unstable trochanteric fractures provides a modest reduction in pain and a slight improvement in the quality of life during the course of healing when compared with conventional fixation with a sliding screw device alone

Aims

Proximal humeral fractures are the third most common fracture among the elderly. Complications associated with fixation include screw perforation, varus collapse, and avascular necrosis of the humeral head. To address these challenges, various augmentation techniques to increase medial column support have been developed. There are currently no recent studies that definitively establish the superiority of augmented fixation over non-augmented implants in the surgical treatment of proximal humeral fractures. The aim of this systematic review and meta-analysis was to compare the outcomes of patients who underwent locking-plate fixation with cement augmentation or bone-graft augmentation versus those who underwent locking-plate fixation without augmentation for proximal humeral fractures.

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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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This meta-analysis and systematic review aimed to comprehensively investigate the effects of vitamin K supplementation on bone mineral density (BMD) at various sites and bone metabolism in middle-aged and older adults.

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The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit.

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The prevalence of scoliosis is not known in patients with idiopathic short stature, and the impact of treatment with recombinant human growth hormone on those with scoliosis remains controversial. We investigated the prevalence of scoliosis radiologically in children with idiopathic short stature, and the impact of treatment with growth hormone in a cross-sectional and retrospective cohort study.

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This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels.

Clinical studies evaluating the effects of vitamin D alone or in combination with calcium on physical function, falls and fractures have been inconsistent. Vitamin D has, however, been the focus of much orthopaedic, trauma and endocrine research. Playing a central role in muscle and bone metabolism, some studies on Vitamin D therapies offer the tantalising suggestion of a reduction in falls and fractures simply with vitamin D supplementation. We review the background and evidence behind vitamin D

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.

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This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes.

The December 2022 Foot & Ankle Roundup³⁶⁰ looks at: Evans calcaneal osteotomy and multiplanar correction in flat foot deformity; Inflammatory biomarkers in tibialis posterior tendon dysfunction; Takedown of ankle fusions and conversion to total ankle arthroplasty; Surgical incision closure with three different materials; Absorbable sutures are not inferior to nonabsorbable sutures for tendo Achilles repair; Zadek’s osteotomy is a reliable technique for treating Haglund’s syndrome; How to best assess patient limitations after acute Achilles tendon injury; Advances in the management of infected nonunion of the foot and ankle.

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Given the possible radiation damage and inaccuracy of radiological investigations, particularly in children, ultrasound and superb microvascular imaging (SMI) may offer alternative methods of evaluating new bone formation when limb lengthening is undertaken in paediatric patients. The aim of this study was to assess the use of ultrasound combined with SMI in monitoring new bone formation during limb lengthening in children.

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Frailty greatly increases the risk of adverse outcome of trauma in older people. Frailty detection tools appear to be unsuitable for use in traumatically injured older patients. We therefore aimed to develop a method for detecting frailty in older people sustaining trauma using routinely collected clinical data.

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Most patients with advanced malignancy suffer bone metastases, which pose a significant challenge to orthopaedic services and burden to the health economy. This study aimed to assess adherence to the British Orthopaedic Oncology Society (BOOS)/British Orthopaedic Association (BOA) guidelines on patients with metastatic bone disease (MBD) in the UK.

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This study aimed to compare the performance of survival prediction models for bone metastases of the extremities (BM-E) with pathological fractures in an Asian cohort, and investigate patient characteristics associated with survival.

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Advances in treatment have extended the life expectancy of patients with metastatic bone disease (MBD). Patients could experience more skeletal-related events (SREs) as a result of this progress. Those who have already experienced a SRE could encounter another local management for a subsequent SRE, which is not part of the treatment for the initial SRE. However, there is a noted gap in research on the rate and characteristics of subsequent SREs requiring further localized treatment, obligating clinicians to extrapolate from experiences with initial SREs when confronting subsequent ones. This study aimed to investigate the proportion of MBD patients developing subsequent SREs requiring local treatment, examine if there are prognostic differences at the initial treatment between those with single versus subsequent SREs, and determine if clinical, oncological, and prognostic features differ between initial and subsequent SRE treatments.

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This study aims to determine the rate of and risk factors for total knee arthroplasty (TKA) after operative management of tibial plateau fractures (TPFs) in older adults.

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Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

A common situation presenting to the orthopaedic surgeon today is a worn acetabular liner with substantial acetabular and pelvic osteolysis. The surgeon has many options for dealing with osteolytic defects. These include allograft, calcium based substitutes, demineralised bone matrix, or combinations of these options with or without addition of platelet rich plasma. To date there are no clinical studies to determine the efficacy of using bone-stimulating materials in osteolytic defects at the time of revision surgery and there are surprisingly few studies demonstrating the clinical efficacy of these treatment options. Even when radiographs appear to demonstrate incorporation of graft material CT studies have shown that incorporation is incomplete. The surgeon, in choosing a graft material for a surgical procedure must take into account the efficacy, safety, cost and convenience of that material. Cite this article: Bone Joint J 2014;96-B (11 Suppl A):70–2

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To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections.

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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.

Cite this article: Bone Joint Res 2023;12(5):311–312.

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Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier.

Aims. Surgical intervention in patients with bone metastases from breast cancer is dependent on the estimated survival of the patient. The purpose of this paper was to identify factors that would predict survival so that specific decisions could be made in terms of surgical (or non-surgical) management. . Methods. The records of 113 consecutive patients (112 women) with metastatic breast cancer were analysed for clinical, radiological, serological and surgical outcomes. Their median age was 61 years (interquartile range 29 to 90) and the median duration of follow-up was 1.6 years (standard deviation (. sd. ) 1.9, 95% confidence interval (CI) 0 to 5.9). The cumulative one- and five-year rates of survival were 68% and 16% (95% Cl 60 to 77 and 95% CI 10 to 26, respectively). . Results. Linear discriminant analysis identified a ‘quadruple A’ predictor of survival by reclassifying the sum of the albumin, adjusted calcium, alkaline phosphatase and age covariates each multiplied by a determined factor. The accuracy of this ‘quadruple A’ predictor was 90% with a sensitivity of 100% and a specificity of 88%. A receiver operating characteristic (ROC) curve revealed an area under the curve of 79%. Survival analysis for this ‘quadruple A’ predictor (<  = one or > one year survival) was statistically significant using the log rank test (p = 0.0004) and Cox proportional hazard (p = 0.001). Multivariate analysis showed the 'quadruple A' predictor to be the only independent predictor of survival (p = 0.01). . Discussion. The 'quadruple A' predictor, together with other positive predictors of survival, can be used by oncologists, orthopaedic and breast surgeons to estimate survival and therefore guide management. Cite this article: Bone Joint J 2016;98-B:266–70

The August 2024 Knee Roundup³⁶⁰ looks at: Calcification’s role in knee osteoarthritis: implications for surgical decision-making; Lower complication rates and shorter lengths of hospital stay with technology-assisted total knee arthroplasty; Revision surgery: the hidden burden on surgeons; Are preoperative weight loss interventions worthwhile?; Total knee arthroplasty with or without prior bariatric surgery: a systematic review and meta-analysis; Aspirin triumphs in knee arthroplasty: a decade of evidence; Efficacy of DAIR in unicompartmental knee arthroplasty: a glimpse from Oxford.

There is a disparity in sport-related injuries between sexes, with females sustaining non-contact musculoskeletal injuries at a higher rate. Anterior cruciate ligament ruptures are between two and eight times more common than in males, and females also have a higher incidence of ankle sprains, patellofemoral pain, and bone stress injuries. The sequelae of such injuries can be devastating to an athlete, resulting in time out of sport, surgery, and the early onset of osteoarthritis. It is important to identify the causes of this disparity and introduce prevention programmes to reduce the incidence of these injuries. A natural difference reflects the effect of reproductive hormones in females, which have receptors in certain musculoskeletal tissues. Relaxin increases ligamentous laxity. Oestrogen decreases the synthesis of collagen and progesterone does the opposite. Insufficient diet and intensive training can lead to menstrual irregularities, which are common in female athletes and result in injury, whereas oral contraception may have a protective effect against certain injuries. It is important for coaches, physiotherapists, nutritionists, doctors, and athletes to be aware of these issues and to implement preventive measures. This annotation explores the relationship between the menstrual cycle and orthopaedic sports injuries in pre-menopausal females, and proposes recommendations to mitigate the risk of sustaining these injuries.

Cite this article: Bone Joint J 2023;105-B(7):723–728.

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This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect.

The April 2012 Research Roundup. 360 . looks at who is capable of being an arthroscopist, bupivacaine, triamcinolone and chondrotoxicity, reducing scarring in injured skeletal muscle, horny Goat Weed and the repair of osseous defects, platelet-derived growth factor and fracture healing, the importance of the reserve zone in a child’s growth plate, coping with advanced arthritis, hydroxyapatite and platelet-rich plasma for bone defects, and calcium phosphate and bone regeneration

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Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration.

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Isolated acetabular liner exchange with a highly crosslinked polyethylene (HXLPE) component is an option to address polyethylene wear and osteolysis following total hip arthroplasty (THA) in the presence of a well-fixed acetabular shell. The liner can be fixed either with the original locking mechanism or by being cemented within the acetabular component. Whether the method used for fixation of the HXLPE liner has any bearing on the long-term outcomes is still unclear.

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The aim of this study was to compare the pattern of initial fixation and changes in periprosthetic bone mineral density (BMD) between patients who underwent total hip arthroplasty (THA) using a traditional fully hydroxyapatite (HA)-coated stem (T-HA group) and those with a newly introduced fully HA-coated stem (N-HA group).

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Calcaneal osteomyelitis remains a difficult condition to treat with high rates of recurrence and below-knee amputation, particularly in the presence of severe soft-tissue destruction. This study assesses the outcomes of single-stage orthoplastic surgical treatment of calcaneal osteomyelitis with large soft-tissue defects.

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The survival of humeral hemiarthroplasties in patients with relatively intact glenoid cartilage could theoretically be extended by minimizing the associated postoperative glenoid erosion. Ceramic has gained attention as an alternative to metal as a material for hemiarthroplasties because of its superior tribological properties. The aim of this study was to assess the in vitro wear performance of ceramic and metal humeral hemiarthroplasties on natural glenoids.

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The primary aim of this study is to assess the survival of the uncemented hydroxyapatite (HA) coated Trident II acetabular component as part of a hybrid total hip arthroplasty (THA) using a cemented Exeter stem. The secondary aims are to assess the complications, joint-specific function, health-related quality of life, and radiological signs of loosening of the acetabular component.