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.

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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.

Metastatic bone disease (MBD) is a significant contributor to diminished quality of life in cancer patients, often leading to pathologic fractures, hypercalcaemia, intractable bone pain, and reduced functional independence. Standard of care management for MBD patients undergoing orthopaedic surgery is multi-disciplinary, includes regular surgical follow-up, case by case assessment for use of bone protective medications, and post-operative radiation therapy to the operative site. The number of patients in southern Alberta receiving standard of care post-operative management is currently unclear. Our aim is to develop a database of all patients in southern Alberta undergoing orthopaedic surgery for MBD and to assess for deficiencies and opportunities to ensure standard of care for this complex patient population. Patients were identified for database inclusion by a search query of the Alberta Cancer Registry of all patients with a diagnosis of metastatic cancer who underwent surgery for an impending or pathologic fracture in the Calgary, South and Central Alberta Zones. Demographic information, primary cancer history, previous local and systemic treatments, anatomical location of MBD event(s), surgical fixation techniques, and post-operative care details were collected. The rate of standard of care post-operative treatment was evaluated. A comparison of outcomes between tertiary urban centres and rural centres was also completed. Survival was calculated from time of first operation to date of death. Univariate and multivariate analyses were performed to identify the impact of post-operative care variables on survival amongst patients surviving longer than one month. We identified 402 patients who have undergone surgical treatment for MBD in southern Alberta from 2006-2018. Median age at time of surgery was 66.3 years and 52.7% of patients were female. Breast, lung, prostate, renal cell and multiple myeloma were the most common primary malignancies (n=328, 81.6%). Median post-operative survival was 6.8 months (95%CI: 5.7-8.3). 203 patients (52.5%) were treated with post-operative radiotherapy and 159 patients (50.8%) had post-operative surgical follow-up. Only 39 patients (11.3%) received bone protective agents in the peri-operative period. On multivariate survival analysis, post-operative surgical follow-up was associated with improved survival (p<0.001). Patients were treated at nine hospitals across southern Alberta with most patients treated in an urban center (65.9%). Post-operative survival was significantly longer amongst patients treated in an urban center (9.0 months, 95%CI: 6.9-12.3 versus 4.3 months, 95%CI: 3.4-5.6, p<0.001). The burden of MBD is significant and increasing. With treatment occurring at multiple provincial sites, there is a need for standardized, primary disease-specific peri- and post-operative protocols to ensure quality and efficacious patient care. To provide evidence informed treatment recommendations, we have developed a database of all patients in southern Alberta undergoing orthopaedic surgery for MBD. Our results demonstrate that many patients were not treated according to post-operative standard of care recommendations. Notably, half of the included patients did not have documented surgical follow-up, post-operative radiation treatment was low and only 11% were actively treated with bone protective agents. This data justifies the need for established surgical MBD care pathways and provides reference data to benchmark prospective QA and QI outcomes in this patient population

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The proximal tibia (PT) is the anatomical site most frequently affected by primary bone tumours after the distal femur. Reconstruction of the PT remains challenging because of the poor soft-tissue cover and the need to reconstruct the extensor mechanism. Reconstructive techniques include implantation of massive endoprosthesis (megaprosthesis), osteoarticular allografts (OAs), or allograft-prosthesis composites (APCs).

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Due to their radiolucency and favourable mechanical properties, carbon fibre nails may be a preferable alternative to titanium nails for oncology patients. We aim to compare the surgical characteristics and short-term results of patients who underwent intramedullary fixation with either a titanium or carbon fibre nail for pathological long-bone fracture.

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The last decade has seen a marked increase in surgical rib fracture fixation (SRF). The evidence to support this comes largely from retrospective cohorts, and adjusting for the effect of other injuries sustained at the same time is challenging. This study aims to assess the impact of SRF after blunt chest trauma using national prospective registry data, while controlling for other comorbidities and injuries.

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The aim of this study was to assess the clinical and radiological outcomes of an antiprotrusio acetabular cage (APC) when used in the surgical treatment of periacetabular bone metastases.

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The aims of this study were to determine the diagnostic yield of image-guided biopsy in providing a final diagnosis in patients with suspected infectious spondylodiscitis, to report the diagnostic accuracy of various microbiological tests and histological examinations in these patients, and to report the epidemiology of infectious spondylodiscitis from a country where tuberculosis (TB) is endemic, including the incidence of drug-resistant TB.

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The effect of pelvic tilt (PT) and sagittal balance in hips with pincer-type femoroacetabular impingement (FAI) with acetabular retroversion (AR) is controversial. It is unclear if patients with AR have a rotational abnormality of the iliac wing. Therefore, we asked: are parameters for sagittal balance, and is rotation of the iliac wing, different in patients with AR compared to a control group?; and is there a correlation between iliac rotation and acetabular version?

Introduction. Patients with metastatic spinal cord compression (MSCC) or unstable spinal lesions warrant early surgical consultation. In multiple myeloma, chemotherapy and radiotherapy have the potential to decompress the spinal canal effectively in the presence of epidural lesions. Mechanical stability conferred by bracing may potentiate intraosseous and extraosseous bone formation, thus increasing spinal stability. This study aims to review the role of non-operative management in myeloma patients with a high degree of spinal instability, in a specialist tertiary centre. Methods. Retrospective analysis of a prospectively collected database of 83 patients with unstable myelomatous lesions of the spine, defined by a Spinal Instability Neoplastic Score (SINS) of 13–18. Data collected include patient demographics, systemic treatment, neurological status, radiological presence of cord compression, most unstable vertebral level and presence of intraosseous and extraosseous bone formation. Post-treatment scores were calculated based on follow-up imaging which was carried out at 2 weeks for cord compression and 12 weeks for spinal instability. A paired t-test was used to identify any significant difference between pre- and post-treatment SINS and linear regression was used to assess the association between variables and the change in SINS. Results. A significant reduction in SINS was observed from a pre-treatment average score of 14 to a score of 9, following treatment for myeloma (p<0.001). A higher initial score and a younger age were associated with a larger overall reduction in SINS (p<0.001 and p=0.02 respectively). No single variable (bisphosphates, chemotherapy, radiotherapy and steroids) had a significant association with SINS reduction. 25 (30%) patients had spinal cord compression, all of which showed radiological resolution of cord compression at 2 weeks. No patients developed neurological deterioration during treatment and all patients had an improvement in their pain scores. 64 (77%) patients had evidence of intraosseous and/or extraosseous bone formation on their follow-up scan. Conclusion. Non-operative management in the form of bracing and systemic therapy is a safe and effective treatment for spinal instability and spinal cord compression in myeloma. Treatment of unstable myelomatous lesions of the spine with or without cord compression should not follow traditional guidelines for MSCC. The decision to adopt a non-operative approach in this cohort of patients should ideally be made in a tertiary centre with expertise in multiple myeloma and in a multidisciplinary setting

Introduction. Spine is a common site for haematological malignancies. Multiple myeloma affects the spine in 70% of cases. New guidelines were published in 2015 to help manage spinal haematological malignancies. Despite neural compression or spinal instability, instrumentation of the spine should be avoided. Surgery carries significant risks of wound complications and more importantly delaying the definitive chemotherapy and radiotherapy. Cement augmentation and bracing for pain and prevention of deformity is key to the new strategies. We aimed to evaluate the different treatment modalities adopted in the spine unit at St George's hospital for spinal haematological malignancies. We compared our practice to the current guidelines published in 2015. Methods. Retrospective review of all spinal haematological malignancy patients who were discussed in the spinal MDT and managed through the spine unit at St George's hospital in the period between April 2019 and February 2021. We analysed the demographics of the patients treated in this period and compared the management modalities adopted in the unit to the current British haematological guidelines. Results. 139 patients were included in this study, 61.9% of them were male. 70 cases came through the MSCC pathway. 15 patients had their spinal involvement in the lumbar spine only below the conus. The Bilsky Grades of the other 124 cases were B0: 35.97 % 1a: 4.31%%, 1b: 7.19%, 1c: 3.59%, 2: 5.75% 3: 32.37%. 43 patients (30.9 %) had neurological deficits on presentation. 70 cases were treated conservatively (50.35%), 21 were treated with brace only (15.1%), 25 had BKP (17.98%) and 23 were treated with instrumentation (16.54%). The number of instrumented cases was small and trending down and cement augmentation and bracing were more frequently chosen for these patients. This comes in accordance to the British haematological guidelines. Conclusion. Utilising BJH 2015 guidelines we have reduced our instrumented operative case load. There is a higher percentage of BKP and Bracing in accordance to the algorithm

Aims. The aim of this study was to assess orthopaedic oncologic patient morbidity resulting from COVID-19 related institutional delays and surgical shutdowns during the first wave of the pandemic in New York, USA. Methods. A single-centre retrospective observational study was conducted of all orthopaedic oncologic patients undergoing surgical evaluation from March to June 2020. Patients were prioritized as level 0-IV, 0 being elective and IV being emergent. Only priority levels 0 to III were included. Delay duration was measured in days and resulting morbidities were categorized into seven groups: prolonged pain/disability; unplanned preoperative radiation and/or chemotherapy; local tumour progression; increased systemic disease; missed opportunity for surgery due to progression of disease/lost to follow up; delay in diagnosis; and no morbidity. Results. Overall, 25 patients met inclusion criteria. There were eight benign tumours, seven metastatic, seven primary sarcomas, one multiple myeloma, and two patients without a biopsy proven diagnosis. There was no priority level 0, two priority level I, six priority level II, and 17 priority level III cases. The mean duration of delay for priority level I was 114 days (84 to 143), priority level II was 88 days (63 to 133), and priority level III was 77 days (35 to 269). Prolonged pain/disability and delay in diagnosis, affecting 52% and 40%,respectively, represented the two most frequent morbidities. Local tumour progression and increased systemic disease affected 32% and 24% respectively. No patients tested positive for COVID-19. Conclusion. COVID-19 related delays in surgical management led to major morbidity in this studied orthopaedic oncologic patient population. By understanding these morbidities through clearer hindsight, a thoughtful approach can be developed to balance the risk of COVID-19 exposure versus delay in treatment, ensuring optimal care for orthopedic oncologic patients as the pandemic continues with intermittent calls for halting surgery. Cite this article: Bone Jt Open 2021;2(4):236–242

Aims

LY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling.

The rate of fracture and subsequent nonunion after radiation therapy for soft-tissue sarcomas and bone tumors has been demonstrated to quite high. There is a paucity of data describing the optimal treatment for these nonunions. Free vascularized fibular grafts (FVFG) have been used successfully in the treatment of large segmental bone defects in the axial and appendicular skeleton, however, their efficacy with respect to treatment of radiated nonunions remains unclear. The purpose of the study was to assess the 1) union rate, 2) clinical outcomes, and 3) complications following FVFG for radiation-induced femoral fracture nonunions. We identified 24 patients who underwent FVFG for the treatment of radiation-induced femoral fracture nonunion between 1991 and 2015. Medical records were reviewed in order to determine oncologic diagnosis, total preoperative radiation dose, type of surgical treatment for the nonunion, clinical outcomes, and postoperative complications. There were 11 males and 13 females, with a mean age of 59 years (range, 29 – 78) and a mean follow-up duration of 61 months (range, 10 – 183 months). Three patients had a history of diabetes mellitus and three were current tobacco users at the time of FVFG. No patient was receiving chemotherapy during recovery from FVFG. Oncologic diagnoses included unspecified soft tissue sarcomas (n = 5), undifferentiated pleomorphic sarcoma (UPS) (n = 3), myxofibrosarcoma (n = 3), liposarcoma (n = 2), Ewing's sarcoma (n = 2), lymphoma (n = 2), hemangiopericytoma, leiomyosarcoma, multiple myeloma, myxoid chondrosarcoma, myxoid liposarcoma, neurofibrosarcoma, and renal cell carcinoma. Mean total radiation dose was 56.3 Gy (range, 39 – 72.5), given at a mean of 10.2 years prior to FVFG. The average FVFG length was 16.4 cm. In addition to FVFG, 13 patients underwent simultaneous autogenous iliac crest bone grafting, nine had other cancellous autografting, one received cancellous allograft, and three were treated with synthetic graft products. The FVFG was fixed as an onlay graft using lag screws in all cases, additional fixation was obtained with an intramedullary nail (n = 19), dynamic compression plate (n = 2), blade plate (n = 2), or lateral locking plate (n = 1). Nineteen (79%) fractures went on to union at a mean of 13.1 months (range, 4.8 – 28.1 months). Musculoskeletal Tumor Society scores improved from eight preoperatively to 22 at latest follow-up (p < 0.0001). Among the five fractures that failed to unite, two were converted to proximal femoral replacements (PFR), two remained stable pseudarthroses, and one was converted to a total hip arthroplasty. A 6th case did unite initially, however, subsequent failure lead to PFR. Seven patients (29%) required a second operative grafting. There were five additional complications including three infections, one wound dehiscence, and one screw fracture. No patient required amputation. Free vascularized fibular grafts are a reliable treatment option for radiation-induced pathologic femoral fracture nonunions, providing a union rate of 79%. Surgeons should remain cognizant, however, of the elevated rate of infectious complications and need for additional operative grafting procedures

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The aim of this study was to present the long-term surgical outcomes, complications, implant survival, and causes of implant failure in patients treated with the modified Harrington procedure using antegrade large diameter pins.

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This study aimed to evaluate the incidence and prognosis of patients with spinal metastasis as the initial manifestation of malignancy (SM-IMM).

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with limited coding potential, which have emerged as novel regulators in many biological and pathological processes, including growth, development, and oncogenesis. Accumulating evidence suggests that lncRNAs have a special role in the osteogenic differentiation of various types of cell, including stem cells from different sources such as embryo, bone marrow, adipose tissue and periodontal ligaments, and induced pluripotent stem cells. Involved in complex mechanisms, lncRNAs regulate osteogenic markers and key regulators and pathways in osteogenic differentiation. In this review, we provide insights into the functions and molecular mechanisms of lncRNAs in osteogenesis and highlight their emerging roles and clinical value in regenerative medicine and osteogenesis-related diseases.

Cite this article: J. Zhang, X. Hao, M. Yin, T. Xu, F. Guo. Long non-coding RNA in osteogenesis: A new world to be explored. Bone Joint Res 2019;8:73–80. DOI: 10.1302/2046-3758.82.BJR-2018-0074.R1.

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions.

Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.

Aims. The aim of this study was to validate the Mirels score in predicting pathological fractures in metastatic disease of the lower limb. Patients and Methods. A total of 62 patients with confirmed metastatic disease met the inclusion criteria. Of the 62 patients, 32 were female and 30 were male. The mean age of patients was 65 years (35 to 89). The primary malignancy originated from the breast in 27 (44%) patients, prostate in 15 (24%) patients, kidney in seven (11%), and lung in four (6%) of patients. One patient (2%) had metastatic carcinoma from the lacrimal gland, two patients (3%) had multiple myeloma, one patient (2%) had lymphoma of bone, and five patients (8%) had metastatic carcinoma of unknown primary. Plain radiographs at the time of initial presentation were scored using Mirels system by the four authors. The radiographic components of the score (anatomical site, size, and radiographic appearance) were scored two weeks apart. Inter- and intraobserver reliability were calculated with Fleiss’ kappa test. Bland-Altman plots were created to compare the variances of the individual components of the score and the total Mirels score. Results. Kappa values for the interobserver variability of the components of the Mirels score were k = 0.554 (95% CI 0.483 to 0.626) for site, k = 0.342 (95% CI 0.285 to 0.400) for size, k = 0.443 (95% CI 0.387 to 0.499) for radiographic appearance, and k = 0.294 (95% CI 0.258 to 0.331)for the total score. Kappa values for the intra-observer reliability were k = 0.608 (95% CI 0.506 to 0.710) for site, k = 0.579 (95% CI 0.487 to 0.670) for size, k = 0.614 (95% CI 0.522 to 0.703) for radiographic appearance, and k = 0.323 (95% CI 0.266 to 0.379) for total score. Conclusion. Our study showed fair to moderate agreement between authors when using the Mirels score, and moderate to substantial agreement when authors rescored radiographs. The Mirels score is subjective and lacks reproducibility in predicting the risk of pathological fracture. Cite this article: Bone Joint J 2018;100-B:1100–5

Objectives

In this prospective cohort study, we investigated whether patient-specific finite element (FE) models can identify patients at risk of a pathological femoral fracture resulting from metastatic bone disease, and compared these FE predictions with clinical assessments by experienced clinicians.