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Bone & Joint Research
Vol. 13, Issue 12 | Pages 725 - 740
5 Dec 2024
Xing J Liu S

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.


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1301 - 1305
1 Nov 2024
Prajapati A Thakur RPS Gulia A Puri A

Aims

Reconstruction after osteoarticular resection of the proximal ulna for tumours is technically difficult and little has been written about the options that are available. We report a series of four patients who underwent radial neck to humeral trochlea transposition arthroplasty following proximal ulnar osteoarticular resection.

Methods

Between July 2020 and July 2022, four patients with primary bone tumours of the ulna underwent radial neck to humeral trochlea transposition arthroplasty. Their mean age was 28 years (12 to 41). The functional outcome was assessed using the range of motion (ROM) of the elbow, rotation of the forearm and stability of the elbow, the Musculoskeletal Tumor Society score (MSTS), and the nine-item abbreviated version of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH-9) score.


Bone & Joint Open
Vol. 5, Issue 9 | Pages 749 - 757
12 Sep 2024
Hajialiloo Sami S Kargar Shooroki K Ammar W Nahvizadeh S Mohammadi M Dehghani R Toloue B

Aims

The ulna is an extremely rare location for primary bone tumours of the elbow in paediatrics. Although several reconstruction options are available, the optimal reconstruction method is still unknown due to the rarity of proximal ulna tumours. In this study, we report the outcomes of osteoarticular ulna allograft for the reconstruction of proximal ulna tumours.

Methods

Medical profiles of 13 patients, who between March 2004 and November 2021 underwent osteoarticular ulna allograft reconstruction after the resection of the proximal ulna tumour, were retrospectively reviewed. The outcomes were measured clinically by the assessment of elbow range of motion (ROM), stability, and function, and radiologically by the assessment of allograft-host junction union, recurrence, and joint degeneration. The elbow function was assessed objectively by the Musculoskeletal Tumor Society (MSTS) score and subjectively by the Toronto Extremity Salvage Score (TESS) and Mayo Elbow Performance Score (MEPS) questionnaire.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 1000 - 1007
1 Sep 2024
Gong T Lu M Sheng H Li Z Zhou Y Luo Y Min L Tu C

Aims

Endoprosthetic reconstruction following distal femur tumour resection has been widely advocated. In this paper, we present the design of an uncemented endoprosthesis system featuring a short, curved stem, with the goal of enhancing long-term survivorship and functional outcomes.

Methods

This study involved patients who underwent implantation of an uncemented distal femoral endoprosthesis with a short and curved stem between 2014 and 2019. Functional outcomes were assessed using the 1993 version of the Musculoskeletal Tumour Society (MSTS-93) score. Additionally, we quantified five types of complications and assessed osseointegration radiologically. The survivorship of the endoprosthesis was evaluated according to two endpoints. A total of 134 patients with a median age of 26 years (IQR 16 to 41) were included in our study. The median follow-up time was 61 months (IQR 56 to 76), and the median functional MSTS-93 was 83% (IQR 73 to 91) postoperatively.


Bone & Joint 360
Vol. 13, Issue 4 | Pages 35 - 37
2 Aug 2024

The August 2024 Oncology Roundup360 looks at: What factors are associated with osteoarthritis after cementation for benign aggressive bone tumour of the knee joint: a systematic review and meta-analysis; Recycled bone grafts treated with extracorporeal irradiation or liquid nitrogen freezing after malignant tumour resection; Intercalary resection of the tibia for primary bone tumours: are vascularized fibula autografts with or without allografts a durable reconstruction?; 3D-printed modular prostheses for the reconstruction of intercalary bone defects after joint-sparing limb salvage surgery for femoral diaphyseal tumours; Factors influencing the outcome of patients with primary Ewing’s sarcoma of the sacrum; The significance of surveillance imaging in children with Ewing’s sarcoma and osteosarcoma; Resection margin and soft-tissue sarcomas of the extremities treated with limb-sparing surgery and postoperative radiotherapy.


Bone & Joint 360
Vol. 13, Issue 3 | Pages 40 - 42
3 Jun 2024

The June 2024 Oncology Roundup360 looks at: Chondrosarcoma of the femur: is local recurrence influenced by the presence of an extraosseous component?; Diagnostic challenges in low-grade central osteosarcoma; Single osteotomy technique for frozen autograft (pedicled freezing) in patients with malignant bone tumours; Unplanned resection for small superficial soft-tissue sarcomas: disastrous or simply bad?; Inactivation and replantation of the knee joint: an infeasible surgical method; Active surveillance of diffuse-type tenosynovial giant cell tumours: a retrospective, multicentre cohort study.


Bone & Joint Open
Vol. 5, Issue 4 | Pages 317 - 323
18 Apr 2024
Zhu X Hu J Lin J Song G Xu H Lu J Tang Q Wang J

Aims

The aim of this study was to investigate the safety and efficacy of 3D-printed modular prostheses in patients who underwent joint-sparing limb salvage surgery (JSLSS) for malignant femoral diaphyseal bone tumours.

Methods

We retrospectively reviewed 17 patients (13 males and four females) with femoral diaphyseal tumours who underwent JSLSS in our hospital.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 136 - 136
1 Apr 2024
Amri R Chelly A Ayedi M Rebaii MA Aifa S Masmoudi S Keskes H


Bone & Joint Research
Vol. 13, Issue 2 | Pages 83 - 90
19 Feb 2024
Amri R Chelly A Ayedi M Rebaii MA Aifa S Masmoudi S Keskes H

Aims. The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG. Methods. A total of 32 GCTB tissue samples were analyzed, and the expression of RANKL, OPG, and RUNX2 was evaluated by quantitative polymerase chain reaction (qPCR). The methylation status of RANKL and OPG was also evaluated by quantitative methylation-specific polymerase chain reaction (qMSP). Results. We found that RANKL and RUNX2 gene expression was upregulated more in recurrent than in non-recurrent GCTB tissues, while OPG gene expression was downregulated more in recurrent than in non-recurrent GCTB tissues. Additionally, we proved that changes in DNA methylation contribute to upregulating the expression of RANKL and downregulating the expression of OPG, which are critical for bone homeostasis and GCTB development. Conclusion. Our results suggest that the overexpression of RANKL/RUNX2 and the lower expression of OPG are associated with recurrence in GCTB patients. Cite this article: Bone Joint Res 2024;13(2):84–91


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 93 - 98
1 Jan 2024
Broida SE Tsoi KM Rose PS Ferguson PC Griffin AM Wunder JS Houdek MT

Aims

The sacroiliac joint (SIJ) is the only mechanical connection between the axial skeleton and lower limbs. Following iliosacral resection, there is debate on whether reconstruction of the joint is necessary. There is a paucity of data comparing the outcomes of patients undergoing reconstruction and those who are not formally reconstructed.

Methods

A total of 60 patients (25 females, 35 males; mean age 39 years (SD 18)) undergoing iliosacral resection were reviewed. Most resections were performed for primary malignant tumours (n = 54; 90%). The mean follow-up for surviving patients was nine years (2 to 19).


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 99 - 106
1 Jan 2024
Khal AA Aiba H Righi A Gambarotti M Atherley O'Meally AO Manfrini M Donati DM Errani C

Aims

Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes.

Methods

We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder’s grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome.


Bone & Joint 360
Vol. 12, Issue 6 | Pages 39 - 42
1 Dec 2023

The December 2023 Oncology Roundup360 looks at: A single osteotomy technique for frozen autograft; Complications, function, and survival of tumour-devitalized autografts used in patients with limb-sparing surgery; Is liquid nitrogen recycled bone and vascular fibula the biological reconstruction of choice?; Solitary pulmonary metastases at first recurrence of osteosarcoma; Is a radiological score able to predict resection-grade chondrosarcoma in primary intraosseous lesions of the long bones?; Open versus core needle biopsy in lower-limb sarcoma – current practice patterns and patient outcomes; Natural history of intraosseous low-grade chondroid lesions of the proximal humerus; Local treatment modalities and event-free survival in patients with localized Ewing’s sarcoma; Awaiting biopsy results in solitary pathological proximal femoral fractures.


Bone & Joint Research
Vol. 12, Issue 11 | Pages 677 - 690
1 Nov 2023
Wang X Jiang W Pan K Tao L Zhu Y

Aims

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

Methods

The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Bmal1 gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. Bmal1 lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene.


Bone & Joint 360
Vol. 12, Issue 4 | Pages 35 - 37
1 Aug 2023

The August 2023 Oncology Roundup360 looks at: Giant cell tumour of bone with secondary aneurysmal bone cyst does not have a higher risk of local recurrence; Is bone marrow aspiration and biopsy helpful in initial staging of extraskeletal Ewing’s sarcoma?; Treatment outcomes of extraskeletal Ewing’s sarcoma; Pathological complete response and clinical outcomes in patients with localized soft-tissue sarcoma treated with neoadjuvant chemoradiotherapy or radiotherapy; Long-term follow-up of patients with low-grade chondrosarcoma in the appendicular skeleton treated by extended curettage and liquid nitrogen; Cancer-specific survival after limb salvage versus amputation in osteosarcoma; Outcome after surgical treatment of dermatofibrosarcoma protuberans: does it require extensive follow-up, and what is an adequate resection margin?; Management of giant cell tumours of the distal radius: a systematic review and meta-analysis


Bone & Joint 360
Vol. 12, Issue 4 | Pages 16 - 20
1 Aug 2023

The August 2023 Knee Roundup. 360. looks at: Curettage and cementation of giant cell tumour of bone: is arthritis a given?; Anterior knee pain following total knee arthroplasty: does the patellar cement-bone interface affect postoperative anterior knee pain?; Nickel allergy and total knee arthroplasty; The use of artificial intelligence for the prediction of periprosthetic joint infection following aseptic revision total knee arthroplasty; Ambulatory unicompartmental knee arthroplasty: development of a patient selection tool using machine learning; Femoral asymmetry: a missing piece in knee alignment; Needle arthroscopy – a benefit to patients in the outpatient setting; Can lateral unicompartmental knees be done in a day-case setting?


The Bone & Joint Journal
Vol. 105-B, Issue 6 | Pages 696 - 701
1 Jun 2023
Kurisunkal V Morris G Kaneuchi Y Bleibleh S James S Botchu R Jeys L Parry MC

Aims

Intra-articular (IA) tumours around the knee are treated with extra-articular (EA) resection, which is associated with poor functional outcomes. We aim to evaluate the accuracy of MRI in predicting IA involvement around the knee.

Methods

We identified 63 cases of high-grade sarcomas in or around the distal femur that underwent an EA resection from a prospectively maintained database (January 1996 to April 2020). Suspicion of IA disease was noted in 52 cases, six had IA pathological fracture, two had an effusion, two had prior surgical intervention (curettage/IA intervention), and one had an osseous metastasis in the proximal tibia. To ascertain validity, two musculoskeletal radiologists (R1, R2) reviewed the preoperative imaging (MRI) of 63 consecutive cases on two occasions six weeks apart. The radiological criteria for IA disease comprised evidence of tumour extension within the suprapatellar pouch, intercondylar notch, extension along medial/lateral retinaculum, and presence of IA fracture. The radiological predictions were then confirmed with the final histopathology of the resected specimens.


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 559 - 567
1 May 2023
Aoude A Nikomarov D Perera JR Ibe IK Griffin AM Tsoi KM Ferguson PC Wunder JS

Aims. Giant cell tumour of bone (GCTB) is a locally aggressive lesion that is difficult to treat as salvaging the joint can be associated with a high rate of local recurrence (LR). We evaluated the risk factors for tumour relapse after treatment of a GCTB of the limbs. Methods. A total of 354 consecutive patients with a GCTB underwent joint salvage by curettage and reconstruction with bone graft and/or cement or en bloc resection. Patient, tumour, and treatment factors were analyzed for their impact on LR. Patients treated with denosumab were excluded. Results. There were 53 LRs (15%) at a mean 30.5 months (5 to 116). LR was higher after curettage (18.4%) than after resection (4.6%; p = 0.008). Neither pathological fracture (p = 0.240), Campanacci grade (p = 0.734), soft-tissue extension (p = 0.297), or tumour size (p = 0.872) affected the risk of recurrence. Joint salvage was possible in 74% of patients overall (262/354), and 98% after curettage alone (262/267). Of 49 patients with LR after curettage, 44 (90%) underwent repeated curettage and joint salvage. For patients treated by curettage, only age less than 30 years (p = 0.042) and location in the distal radius (p = 0.043) predicted higher LR. The rate of LR did not differ whether cement or bone graft was used (p = 0.753), but may have been reduced by the use of hydrogen peroxide (p = 0.069). Complications occurred in 15.3% of cases (54/354) and did not differ by treatment. Conclusion. Most patients with a GCTB can undergo successful joint salvage by aggressive curettage, even in the presence of a soft-tissue mass, pathological fracture, or a large lesion, with an 18.4% risk of local recurrence. However, 90% of local relapses after curettage can be treated by repeat joint salvage. Maximizing joint salvage is important to optimize long-term function since most patients with a GCTB are young adults. Younger patients and those with distal radius tumours treated with joint-sparing procedures have a higher rate of local relapse and may require more aggressive treatment and closer follow-up. Cite this article: Bone Joint J 2023;105-B(5):559–567


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 551 - 558
1 May 2023
Wang H Ji T Qu H Yan T Li D Yang R Tang X Guo W

Aims. The aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours. Methods. ICG fluorescence imaging was performed during surgery in 34 patients with bone and soft-tissue tumours. ICG was administered intravenously at a dose of 2 mg/kg over a period of 60 minutes on the day prior to surgery. The tumour stain rate and signal-to-background ratio of each tumour were post hoc analyzed. After tumour resection, the tumour bed was scanned to locate sites with fluorescence residuals, which were subsequently inspected and biopsied. Results. The overall tumour stain rate was 88% (30/34 patients), and specific stain rates included 90% for osteosarcomas and 92% for giant cell tumours. For malignant tumours, the overall stain rate was 94%, while it was 82% for benign tumours. The ICG tumour stain was not influenced by different pathologies, such as malignant versus benign pathology, the reception (or lack thereof) of neoadjuvant chemotherapies, the length of time between drug administration and surgery, the number of doses of denosumab for patients with giant cell tumours, or the tumour response to neoadjuvant chemotherapy. The overall accuracy rate of successfully predicting tumour residuals using fluorescence was 49% (23/47 pieces of tissue). The accuracy rate after en bloc resection was significantly lower than that after piecemeal resection (16% vs 71%; p < 0.001). Conclusion. A high percentage of bone and soft-tissue tumours can be stained by ICG and the tumour staining with ICG was stable. This approach can be used in both benign and malignant tumours, regardless of whether neoadjuvant chemotherapy is adopted. The technique is also useful to detect tumour residuals in the wound, especially in patients undergoing piecemeal resection. Cite this article: Bone Joint J 2023;105-B(5):551–558


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 18 - 18
11 Apr 2023
Kühl J Gorb S Klüter T Naujokat H Seekamp A Fuchs S
Full Access

Critical-sized bone defects can result from trauma, inflammation, and tumor resection. Such bone defects, often have irregular shapes, resulting in the need for new technologies to produce suitable implants. Bioprinting is an additive manufacturing method to create complex and individualised bone constructs, which can already include vital cells. In this study, we established an extrusion-based printing technology to produce osteoinductive scaffolds based on polycaprolactone (PCL) combined with calcium phosphate, which is known to induce osteogenic differentiation of stem cells. The model was created in python based on the signed distance functions. The shape of the 3D model is a ring with a diameter of 20 mm and a height of 10 mm with a spongiosa-like structure. The interconnected irregular pores have a diameter of 2 mm +/− 0.2 mm standard deviation. Extrusion-based printing was performed using the BIO X6. To produce the bioink, PCL (80 kDa) was combined with calcium phosphate nanopowder (> 150 nm particle size) under heating. After printing, 5 × 10. 6. hMSC were seeded on the construct using a rotating incubator. We were able to print a highly accurate ring construct with an interconnected pore structure. The PCL combined with calcium phosphate particles resulted in a precise printed construct, which corresponded to the 3D model. The bioink containing calcium phosphate nanoparticles had a higher printing accuracy compared to PCL alone. We found that hMSC cultured on the construct settled in close proximity to the calcium phosphate particles. The hMSC were vital for 22 days on the construct as demonstrated by life/dead staining. The extrusion printing technology enables to print a mechanically stable construct with a spongiosa-like structure. The porous PCL ring could serve as an outer matrix for implants, providing the construct the stability of natural bone. To extend this technology and to improve the implant properties, a biologised inner structure will be integrated into the scaffold in the future


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 50 - 50
4 Apr 2023
Wang Z van den Beucken J van den Geest I Leeuwenburgh S
Full Access

Residual tumor cells left in the bone defect after malignant bone tumor resection can result in local tumor recurrence and high mortality. Therefore, ideal bone filling materials should not only aid bone reconstruction or regeneration, but also exert local chemotherapeutic efficacy. However, common bone substitutes used in clinics are barely studied in research for local delivery of chemotherapeutic drugs. Here, we aimed to use facile manufacturing methods to render polymethylmethacrylate (PMMA) cement and ceramic granules suitable for local delivery of cisplatin to limit bone tumor recurrence. Porosity was introduced into PMMA cement by adding 1-4% carboxymethylcellulose (CMC) containing cisplatin, and chemotherapeutic activity was rendered to two types of granules via adsorption. Then, mechanical properties, porosity, morphology, drug release kinetics, ex vivo reconstructive properties of porous PMMA and in vitro anti-cancer efficacy against osteosarcoma cells were assessed. Morphologies, molecular structures, drug release profiles and in vitro cytostatic effects of two different drug-loaded granules on the proliferation of metastatic bone tumor cells were investigated. The mechanical strengths of PMMA-based cements were sufficient for tibia reconstruction at CMC contents lower than 4% (≤3%). The concentrations of released cisplatin (12.1% and 16.6% from PMMA with 3% and 4% CMC, respectively) were sufficient for killing of osteosarcoma cells, and the fraction of dead cells increased to 91.3% within 7 days. Functionalized xenogeneic granules released 29.5% of cisplatin, but synthetic CaP granules only released 1.4% of cisplatin over 28 days. The immobilized and released cisplatin retained its anti-cancer efficacy and showed dose-dependent cytostatic effects on the viability of metastatic bone tumor cells. Bone substitutes can be rendered therapeutically active for anticancer efficacy by functionalization with cisplatin. As such, our data suggest that multi-functional PMMA-based cements and cisplatin-loaded granules represent viable treatment options for filling bone defects after bone tumor resection