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The Bone & Joint Journal
Vol. 104-B, Issue 3 | Pages 359 - 367
1 Mar 2022
Deere K Matharu GS Ben-Shlomo Y Wilkinson JM Blom AW Sayers A Whitehouse MR

Aims. A recent report from France suggested an association between the use of cobalt-chrome (CoCr) femoral heads in total hip arthroplasties (THAs) and an increased risk of dilated cardiomyopathy and heart failure. CoCr is a commonly used material in orthopaedic implants. If the reported association is causal, the consequences would be significant given the millions of joint arthroplasties and other orthopaedic procedures in which CoCr is used annually. We examined whether CoCr-containing THAs were associated with an increased risk of all-cause mortality, heart outcomes, cancer, and neurodegenerative disorders in a large national database. Methods. Data from the National Joint Registry was linked to NHS English hospital inpatient episodes for 374,359 primary THAs with up to 14.5 years' follow-up. We excluded any patients with bilateral THAs, knee arthroplasties, indications other than osteoarthritis, aged under 55 years, and diagnosis of one or more outcome of interest before THA. Implants were grouped as either containing CoCr or not containing CoCr. The association between implant construct and the risk of all-cause mortality and incident heart failure, cancer, and neurodegenerative disorders was examined. Results. There were 158,677 individuals (42.4%) with an implant containing CoCr. There were 47,963 deaths, 27,332 heart outcomes, 35,720 cancers, and 22,025 neurodegenerative disorders. There was no evidence of an association between patients with CoCr implants and higher rates of any of the outcomes. Conclusion. CoCr-containing THAs did not have an increased risk of all-cause mortality, or clinically meaningful heart outcomes, cancer, or neurodegenerative disorders into the second decade post-implantation. Our findings will help reassure clinicians and the increasing number of patients receiving primary THA worldwide that the use of CoCr-containing implants is not associated with significant adverse systemic effects. Cite this article: Bone Joint J 2022;104-B(3):359–367



The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 365 - 371
1 Apr 2024
Ledford CK Shirley MB Spangehl MJ Berry DJ Abdel MP

Aims. Breast cancer survivors have known risk factors that might influence the results of total hip arthroplasty (THA) or total knee arthroplasty (TKA). This study evaluated clinical outcomes of patients with breast cancer history after primary THA and TKA. Methods. Our total joint registry identified patients with breast cancer history undergoing primary THA (n = 423) and TKA (n = 540). Patients were matched 1:1 based upon age, sex, BMI, procedure (hip or knee), and surgical year to non-breast cancer controls. Mortality, implant survival, and complications were assessed via Kaplan-Meier methods. Clinical outcomes were evaluated via Harris Hip Scores (HHSs) or Knee Society Scores (KSSs). Mean follow-up was six years (2 to 15). Results. Breast cancer patient survival at five years was 92% (95% confidence interval (CI) 89% to 95%) after THA and 94% (95% CI 92% to 97%) after TKA. Breast and non-breast cancer patients had similar five-year implant survival free of any reoperation or revision after THA (p ≥ 0.412) and TKA (p ≥ 0.271). Breast cancer patients demonstrated significantly lower survival free of any complications after THA (91% vs 96%, respectively; hazard ratio = 2 (95% CI 1.1 to 3.4); p = 0.017). Specifically, the rate of intraoperative fracture was 2.4% vs 1.4%, and venous thromboembolism (VTE) was 1.4% and 0.5% for breast cancer and controls, respectively, after THA. No significant difference was noted in any complications after TKA (p ≥ 0.323). Both breast and non-breast cancer patients experienced similar improvements in HHSs (p = 0.514) and KSSs (p = 0.132). Conclusion. Breast cancer survivors did not have a significantly increased risk of mortality or reoperation after primary THA and TKA. However, there was a two-fold increased risk of complications after THA, including intraoperative fracture and VTE. Cite this article: Bone Joint J 2024;106-B(4):365–371


Bone & Joint Research
Vol. 10, Issue 5 | Pages 310 - 320
3 May 2021
Choi J Lee YS Shim DM Lee YK Seo SW

Aims. Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. Methods. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses. Results. GNAQ-knockdown showed down-regulation of tumour growth through mitogen-activated protein kinase (MAPK) signalling in lung cancer cells, but not increased apoptosis. We found that GNAQ-knockdown induced EMT and promoted invasiveness. GNAQ-knockdown cells injected into the bone marrow of murine tibia induced tumour growth and bone-to-lung metastasis, whereas it did not in control mice. Moreover, the knockdown of GNAQ enhanced cancer stem cell-like properties in lung cancer cells, which resulted in the development of resistance to chemotherapy. Conclusion. The present study reveals that the GNAQ-knockdown induced cancer stem cell-like properties. Cite this article: Bone Joint Res 2021;10(5):310–320


Bone & Joint Research
Vol. 9, Issue 1 | Pages 29 - 35
1 Jan 2020
Choi J Lee YS Shim DM Seo SW

Aims. Receptor activator of nuclear factor-κB ligand (RANKL) is a key molecule that is expressed in bone stromal cells and is associated with metastasis and poor prognosis in many cancers. However, cancer cells that directly express RANKL have yet to be unveiled. The current study sought to evaluate how a single subunit of G protein, guanine nucleotide-binding protein G(q) subunit alpha (GNAQ), transforms cancer cells into RANKL-expressing cancer cells. Methods. We investigated the specific role of GNAQ using GNAQ wild-type cell lines (non-small-cell lung cancer cell lines; A549 cell lines), GNAQ knockdown cell lines, and patient-derived cancer cells. We evaluated GNAQ, RANKL, macrophage colony-stimulating factor (M-CSF), nuclear transcription factor-κB (NF-κB), inhibitor of NF-κB (IκB), and protein kinase B (Akt) signalling in the GNAQ wild-type and the GNAQ-knockdown cells. Osteoclastogenesis was also evaluated in both cell lines. Results. In the GNAQ-knockdown cells, RANKL expression was significantly upregulated (p < 0.001). The expression levels of M-CSF were also significantly increased in the GNAQ-knockdown cells compared with control cells (p < 0.001). GNAQ knockdown cells were highly sensitive to tumour necrosis factor alpha (TNF-α) and showed significant activation of the NF-κB pathway. The expression levels of RANKL were markedly increased in GNAQ mutant compared with GNAQ wild-type in patient-derived tumour tissues. Conclusion. The present study reveals that the alterations of GNAQ activate NF-κB pathway in cancers, which increase RANKL and M-CSF expression and induce osteoclastogenesis in cancers. Cite this article:Bone Joint Res. 2020;9(1):29–35


Bone & Joint Research
Vol. 11, Issue 10 | Pages 715 - 722
10 Oct 2022
Matsuyama Y Nakamura T Yoshida K Hagi T Iino T Asanuma K Sudo A

Aims. Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. Methods. We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated. Results. The viability of LM8, MDA-MB-231, and PC-3 cells strongly decreased at AO concentration of 1.0 μg/ml and a radiation dose of 5 Gy. In xenograft mouse model, the AO-RDT also showed a strong cytocidal effect on tumour at the backside in osteosarcoma, breast cancer, and prostate cancer. AO-RDT treatment was more effective for tumour control than radiotherapy in breast cancer. Conclusion. AO-RDT was effective in preventing the proliferation of osteosarcoma, breast cancer, and prostate cancer cell lines in vitro. The reduction in tumour volume by AO-RDT was also confirmed in vivo. Cite this article: Bone Joint Res 2022;11(10):715–722


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 9 | Pages 1249 - 1251
1 Sep 2009
Huang K Yang R Hsieh C

Breast cancer is generally managed surgically with adjuvant agents which include hormone therapy, chemotherapy, radiotherapy and bisphosphonate therapy. However, some of these adjuvant therapies may cause adverse events, including wound infection, neutropenia, bone marrow suppression and fever. The simultaneous presentation of osteonecrosis and osteomyelitis has not previously been described in patients with breast cancer undergoing hormone therapy and chemotherapy. We report a patient with breast cancer who developed bone infarcts in both legs as well as osteomyelitis in the right distal tibia after treatment which included a modified radical mastectomy, hormone therapy and chemotherapy. Simultaneous osteonecrosis and osteomyelitis should be considered in patients with breast cancer who are receiving chemotherapy and hormone therapy who present with severe bone pain, especially if there have been infective episodes during treatment


Bone & Joint Open
Vol. 5, Issue 4 | Pages 350 - 360
23 Apr 2024
Wang S Chen Z Wang K Li H Qu H Mou H Lin N Ye Z

Aims. Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS. Methods. A retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis. Results. Overall, 123 patients with 127 spinal metastases from NSCLC who underwent decompression surgery followed by postoperative systemic therapy were included. A total of 43 lesions were treated with stereotactic body radiotherapy (SBRT) after surgery and 84 lesions were not. Survival rate at one, two, and three years was 83.4%, 58.9%, and 48.2%, respectively, and LC rate was 87.8%, 78.8%, and 78.8%, respectively. Histological type was the only significant associated factor for both LC (p = 0.007) and OS (p < 0.001). Treatment with targeted therapy was significantly associated with longer survival (p = 0.039). The risk factors associated with worse survival were abnormal laboratory data (p = 0.021), lesions located in the thoracic spine (p = 0.047), and lumbar spine (p = 0.044). This study also revealed that postoperative radiotherapy had little effect in improving OS or LC. Conclusion. Tumour histological type was significantly associated with the prognosis in spinal NSCLC metastasis patients. In the presence of post-surgical systemic therapy, radiotherapy appeared to be less effective in improving LC, OS, or quality of life in spinal NSCLC metastasis patients. Cite this article: Bone Jt Open 2024;5(4):350–360


Bone & Joint Research
Vol. 11, Issue 5 | Pages 278 - 291
12 May 2022
Hu X Fujiwara T Houdek MT Chen L Huang W Sun Z Sun Y Yan W

Aims. Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma. Methods. We reviewed 4,739 patients diagnosed with primary bone sarcomas from the Surveillance, Epidemiology and End Results (SEER) registry between 2007 and 2015. We examined the impact of race and insurance status associated with the presence of metastatic disease at diagnosis, treatment outcome, and overall survival (OS). Results. Patients with Medicaid (odds ratio (OR) 1.41; 95% confidence interval (CI) 1.15 to 1.72) and uninsured patients (OR 1.90; 95% CI 1.26 to 2.86) had higher risks of metastatic disease at diagnosis compared to patients with health insurance. Compared to White patients, Black (OR 0.63, 95% CI 0.47 to 0.85) and Asian/Pacific Islander (OR 0.65, 95% CI 0.46 to 0.91) were less likely to undergo surgery. In addition, Black patients were less likely to receive chemotherapy (OR 0.67, 95% CI 0.49 to 0.91) compared to White patients. In patients with chondrosarcoma, those with Medicaid had worse OS compared to patients with insurance (hazard ratio (HR) 1.65, 95% CI 1.06 to 2.56). Conclusion. In patients with a bone sarcoma, the cancer stage at diagnosis varied based on insurance status, and racial disparities were identified in treatment. Further studies are needed to identify modifiable factors which can mitigate socioeconomic and racial disparities found in patients with bone sarcomas. Cite this article: Bone Joint Res 2022;11(5):278–291


The Journal of Bone & Joint Surgery British Volume
Vol. 77-B, Issue 3 | Pages 345 - 350
1 May 1995
Mathiesen E Ahlbom A Bermann G Lindgren J

The incidence of cancer after hip replacement was studied in the 1.6 million inhabitants of Stockholm County, Sweden. A cohort of 10,785 individuals who had had hip replacement between 1974 and 1988 was followed from the date of operation to the first malignant tumour, to death, or to the end of 1989. The follow-up was based on 58,437 person-years at risk as calculated from information obtained by record-linkage with the National Cancer Registry and the National Cause-of-Death Register. The Standardised Morbidity Ratio (SMR) for all cancer sites, disregarding the length of follow-up, was 0.96 (95% CI 0.90 to 1.03). For lymphoma and leukaemia the corresponding SMR was 0.89 (0.68 to 1.14). Our results do not support previous suggestions of an increased incidence of leukaemia and lymphoma after total hip replacement


The Bone & Joint Journal
Vol. 105-B, Issue 11 | Pages 1206 - 1215
1 Nov 2023
Ladegaard TH Sørensen MS Petersen MM

Aims. We first sought to compare survival for patients treated surgically for solitary and multiple metastases in the appendicular skeleton, and second, to explore the role of complete and incomplete resection (R0 and R1/R2) in patients with a solitary bony metastasis in the appendicular skeleton. Methods. We conducted a retrospective study on a population-based cohort of all adult patients treated surgically for bony metastases of the appendicular skeleton between January 2014 and December 2019. We excluded patients in whom the status of bone metastases and resection margin was unknown. Patients were followed until the end of the study or to their death. We had no loss to follow-up. We used Kaplan-Meier analysis (with log-rank test) to evaluate patient survival. We identified 506 operations in 459 patients. A total of 120 operations (in 116 patients) were for solitary metastases and 386 (in 345 patients) for multiple metastases. Of the 120 operations, 70 (in 69 patients) had no/an unknown status of visceral metastases (solitary group) and 50 (in 49 patients) had visceral metastases. In the solitary group, 45 operations (in 44 patients) were R0 (resections for cure or complete remission) and 25 (in 25 patients) were R1/R2 (resections leaving microscopic or macroscopic tumour, respectively). The most common types of cancer in the solitary group were kidney (n = 27), lung (n = 25), and breast (n = 20). Results. The one-year patient survival was 47% (95% confidence interval (CI) 38 to 57) for the solitary bony metastases and 34% (95% CI 29 to 39) for multiple bone metastases (p < 0.001). The one-year patient survival was 64% (95% CI 52 to 75) for solitary bony metastases without/with unknown visceral metastases and 23% (95% CI 11 to 36) for solitary bony metastases with visceral metastases (p < 0.001). The one-year patient survival was 75% (95% CI 62 to 89) for a solitary bony metastasis after R0 surgery and 42% (95% CI 22 to 61) for a solitary bony metastasis with R1/R2 surgery (p < 0.001). Conclusion. Our study suggests that the surgical treatment of patients with a solitary bony metastasis to the appendicular skeleton results in better survival than for patients with multiple bony metastases. Furthermore, aggressive treatment of a solitary bony metastasis with R0 surgery may improve patient survival. Cite this article: Bone Joint J 2023;105-B(11):1206–1215


The Journal of Bone & Joint Surgery British Volume
Vol. 33-B, Issue 2 | Pages 167 - 179
1 May 1951
Gillis L Lee S

A patient with a chronic discharging sinus or an extensive adherent scar is never safe from the risk of malignant change. Examples are still occurring more than thirty years after the end of the first world war. The possibility should be kept in mind by those concerned with the long-term treatment of wounds of this kind. Reasonable prophylactic measures would be: excision of adherent or unstable scars with, if necessary, their replacement by suitable pedicle flaps having a good blood supply; and earlier amputation if a osteomyelitic sinus persists for several years and does not yield to treatment. Supervision of doubtful cases should be frequent and should not be relaxed with the passage of the years. Warty changes or indolent ulceration of scars should be regarded with grave suspicion and investigated by biopsy. Any increase in pain or discharge in association with a sinus should receive prompt attention. Finally, if malignant change supervenes, treatment should be as speedy and as radical as with any other cancer. At least thirteen of our twenty-four patients have died of cancer


The Journal of Bone & Joint Surgery British Volume
Vol. 74-B, Issue 6 | Pages 883 - 886
1 Nov 1992
Porter D Holden S Steel C Cohen B Wallace M Reid R

We studied the pedigrees of 17 index patients with osteosarcoma, recording malignant disease and cause of death for first- and second-degree relatives. There were seven cancers and five cancer deaths per 2151.5 person-years in first-degree relatives of osteosarcoma patients under the age of 50 years, a significantly greater incidence than in an age- and sex-matched population group (p < 0.001). This excess of malignancy was largely due to two families which fulfilled the criteria for the Li-Fraumeni cancer family syndrome. Both of these families were shown to have the genetic alterations in the p53 gene which have been implicated in this syndrome. Our study suggests that orthopaedic surgeons seeing new cases of osteosarcoma should arrange screening for familial malignancy


The Journal of Bone & Joint Surgery British Volume
Vol. 70-B, Issue 4 | Pages 539 - 542
1 Aug 1988
Gillespie W Frampton C Henderson R Ryan P

We have studied the incidence of tumours at remote sites following total hip replacement: 1,358 individuals have been followed up for 14,286 person-years after operation. In the decade following implantation the incidence of tumours of the lymphatic and haemopoietic systems was significantly greater, and that of cancer of the breast, colon, and rectum, significantly less than expected. Whilst the association might be due in part to an effect of the prosthetic implants, other mechanisms, particularly drug therapy, require consideration


Bone & Joint Research
Vol. 13, Issue 9 | Pages 497 - 506
16 Sep 2024
Hsieh H Yen H Hsieh W Lin C Pan Y Jaw F Janssen SJ Lin W Hu M Groot O

Aims

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.

Methods

This retrospective study included 3,814 adult patients who received local treatment – surgery and/or radiotherapy – for bone metastasis between 1 January 2010 and 31 December 2019. All included patients had at least one SRE requiring local treatment. A subsequent SRE was defined as a second SRE requiring local treatment. Clinical, oncological, and prognostic features were compared between single SREs and subsequent SREs using Mann-Whitney U test, Fisher’s exact test, and Kaplan–Meier curve.


Bone & Joint Research
Vol. 12, Issue 5 | Pages 311 - 312
5 May 2023
Xu C Liu Y

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


Bone & Joint 360
Vol. 11, Issue 3 | Pages 14 - 17
1 Jun 2022


Bone & Joint 360
Vol. 11, Issue 2 | Pages 5 - 10
1 Apr 2022
Zheng A Rocos B


Bone & Joint Open
Vol. 4, Issue 9 | Pages 689 - 695
7 Sep 2023
Lim KBL Lee NKL Yeo BS Lim VMM Ng SWL Mishra N

Aims

To determine whether side-bending films in scoliosis are assessed for adequacy in clinical practice; and to introduce a novel method for doing so.

Methods

Six surgeons and eight radiographers were invited to participate in four online surveys. The generic survey comprised erect and left and right bending radiographs of eight individuals with scoliosis, with an average age of 14.6 years. Respondents were asked to indicate whether each bending film was optimal (adequate) or suboptimal. In the first survey, they were also asked if they currently assessed the adequacy of bending films. A similar second survey was sent out two weeks later, using the same eight cases but in a different order. In the third survey, a guide for assessing bending film adequacy was attached along with the radiographs to introduce the novel T1-45B method, in which the upper endplate of T1 must tilt ≥ 45° from baseline for the study to be considered optimal. A fourth and final survey was subsequently conducted for confirmation.


The Journal of Bone & Joint Surgery British Volume
Vol. 58-B, Issue 4 | Pages 412 - 417
1 Nov 1976
Larsson S Lorentzon R Boquist L

The clinical records, radiographs and histopathological material of all forty-one patients recorded as suffering from fibrosarcoma of bone in the Swedish Cancer Registry for the years 1958 to 1968 have been analysed; in addition, four cases were found on histological review of a series of osteosarcomas. From this re-examination, twenty-four patients with genuine fibrosarcoma of bone were identified; twenty-two had primary neoplasms and two secondary. No sex or geographical differences were found. The tumours showed a prevalence for patients in the adult and older age groups. Half of the tumours arose from femoral or tibial metaphysial bone adjacent to a knee joint. All the tumours were of the medullary type. Almost one-third presented with a pathological fracture, and soft-tissue extension had occurred in all but three tumours. In contrast to previous reports, these tumours were more malignant than osteosarcomas and showed a five-year survival rate of only 4-2 per cent. In accessible sites, ablative surgery was used as the primary treatment, Fibrosarcoma of bone is a distinctive lesion and should be distinguished carefully from periosteal and soft-tissue fibrosarcomas because of differences in prognosis and treatment


The Bone & Joint Journal
Vol. 104-B, Issue 1 | Pages 177 - 182
1 Jan 2022
Hartley LJ AlAqeel M Kurisunkal VJ Evans S

Aims

Current literature suggests that survival outcomes and local recurrence rates of primary soft-tissue sarcoma diagnosed in the very elderly age range, (over 90 years), are comparable with those in patients diagnosed under the age of 75 years. Our aim is to quantify these outcomes with a view to rationalizing management and follow-up for very elderly patients.

Methods

Retrospective access to our prospectively maintained oncology database yielded a cohort of 48 patients across 23 years with a median follow-up of 12 months (0 to 78) and mean age at diagnosis of 92 years (90 to 99). Overall, 42 of 48 of 48 patients (87.5%) were managed surgically with either limb salvage or amputation.


Bone & Joint Research
Vol. 10, Issue 9 | Pages 602 - 610
24 Sep 2021
Tsoi KM Gokgoz N Darville-O'Quinn P Prochazka P Malekoltojari A Griffin AM Ferguson PC Wunder JS Andrulis IL

Aims

Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients.

Methods

Matched tumour and blood were collected from 64 sarcoma patients (n = 70 samples) prior to resection of the primary tumour (n = 57) or disease recurrence (n = 7). DNA was isolated from plasma, quantified, and analyzed for cfDNA. A subset of cases (n = 6) underwent whole exome sequencing to identify tumour-specific alterations used to detect ctDNA using digital droplet polymerase chain reaction (ddPCR).


The Bone & Joint Journal
Vol. 103-B, Issue 9 | Pages 1541 - 1549
1 Sep 2021
Fujiwara T Evans S Stevenson J Tsuda Y Gregory J Grimer RJ Abudu S

Aims

While a centralized system for the care of patients with a sarcoma has been advocated for decades, regional variations in survival remain unclear. The aim of this study was to investigate regional variations in survival and the impact of national policies in patients with a soft-tissue sarcoma (STS) in the UK.

Methods

The study included 1,775 patients with a STS who were referred to a tertiary sarcoma centre. The geographical variations in survival were evaluated according to the periods before and after the issue of guidance by the National Institute for Health and Care Excellence (NICE) in 2006 and the relevant evolution of regional management.


The Journal of Bone & Joint Surgery British Volume
Vol. 78-B, Issue 4 | Pages 680 - 680
1 Jul 1996
GILLESPIE WJ DOORN P


The Journal of Bone & Joint Surgery British Volume
Vol. 79-B, Issue 4 | Pages 702 - 702
1 Jul 1997
Laurence A


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 2 | Pages 225 - 227
1 Feb 2008
Reigstad O Siewers P

An 86-year-old male presented with a loose total hip replacement (THR) ten years after implantation. At revision for anticipated aseptic loosening, watery pus was found in the joint and Bacille-Calmette-Guérin (BCG) was seen on culture. The bacterial strain was identified and was identical to the BCG used in the intravesicular treatment of superficial bladder carcinoma in this patient ten months earlier. After revision he received a full course of antituberculous treatment.

The clinical and radiological results were excellent after follow-up for 30 months with his uncemented THR showing satisfactory incorporation. His inflammatory markers were normal and his Harris hip score was 95 points.

The diagnosis of a tuberculous infection can be easily missed, but must be considered, especially if sterile pus is encountered.


The Bone & Joint Journal
Vol. 99-B, Issue 4 | Pages 516 - 521
1 Apr 2017
Willeumier JJ van der Hoeven NMA Bollen L Willems LNA Fiocco M van der Linden YM Dijkstra PDS

Aims

This study aims to assess first, whether mutations in the epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (kRAS) genes are associated with overall survival (OS) in patients who present with symptomatic bone metastases from non-small cell lung cancer (NSCLC) and secondly, whether mutation status should be incorporated into prognostic models that are used when deciding on the appropriate palliative treatment for symptomatic bone metastases.

Patients and Methods

We studied 139 patients with NSCLC treated between 2007 and 2014 for symptomatic bone metastases and whose mutation status was known. The association between mutation status and overall survival was analysed and the results applied to a recently published prognostic model to determine whether including the mutation status would improve its discriminatory power.




The Bone & Joint Journal
Vol. 106-B, Issue 2 | Pages 203 - 211
1 Feb 2024
Park JH Won J Kim H Kim Y Kim S Han I

Aims. 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. Methods. This retrospective cohort study included 469 patients, who underwent surgery for BM-E between January 2009 and March 2022 at a tertiary hospital in South Korea. Postoperative survival was calculated using the PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models. Model performance was assessed with area under the curve (AUC), calibration curve, Brier score, and decision curve analysis. Cox regression analyses were performed to evaluate the factors contributing to survival. Results. The SORG model demonstrated the highest discriminatory accuracy with AUC (0.80 (95% confidence interval (CI) 0.76 to 0.85)) at 12 months. In calibration analysis, the PATHfx3.0 and OPTIModel models underestimated survival, while the SPRING13 and IOR models overestimated survival. The SORG model exhibited excellent calibration with intercepts of 0.10 (95% CI -0.13 to 0.33) at 12 months. The SORG model also had lower Brier scores than the null score at three and 12 months, indicating good overall performance. Decision curve analysis showed that all five survival prediction models provided greater net benefit than the default strategy of operating on either all or no patients. Rapid growth cancer and low serum albumin levels were associated with three-, six-, and 12-month survival. Conclusion. State-of-art survival prediction models for BM-E (PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models) are useful clinical tools for orthopaedic surgeons in the decision-making process for the treatment in Asian patients, with SORG models offering the best predictive performance. Rapid growth cancer and serum albumin level are independent, statistically significant factors contributing to survival following surgery of BM-E. Further refinement of survival prediction models will bring about informed and patient-specific treatment of BM-E. Cite this article: Bone Joint J 2024;106-B(2):203–211


Bone & Joint Open
Vol. 4, Issue 11 | Pages 817 - 824
1 Nov 2023
Filis P Varvarousis D Ntritsos G Dimopoulos D Filis N Giannakeas N Korompilias A Ploumis A

Aims. The standard of surgical treatment for lower limb neoplasms had been characterized by highly interventional techniques, leading to severe kinetic impairment of the patients and incidences of phantom pain. Rotationplasty had arisen as a potent limb salvage treatment option for young cancer patients with lower limb bone tumours, but its impact on the gait through comparative studies still remains unclear several years after the introduction of the procedure. The aim of this study is to assess the effect of rotationplasty on gait parameters measured by gait analysis compared to healthy individuals. Methods. The MEDLINE, Scopus, and Cochrane databases were systematically searched without time restriction until 10 January 2022 for eligible studies. Gait parameters measured by gait analysis were the outcomes of interest. Results. Three studies were eligible for analyses. Compared to healthy individuals, rotationplasty significantly decreased gait velocity (-1.45 cm/sec; 95% confidence interval (CI) -1.98 to -0.93; p < 0.001), stride length (-1.20 cm; 95% CI -2.31 to -0.09; p < 0.001), cadence (-0.83 stride/min; 95% (CI -1.29 to -0.36; p < 0.001), and non-significantly increased cycle time (0.54 sec; 95% CI -0.42 to 1.51; p = 0.184). Conclusion. Rotationplasty is a valid option for the management of lower limb bone tumours in young cancer patients. Larger studies, with high patient accrual, refined surgical techniques, and well planned rehabilitation strategies, are required to further improve the reported outcomes of this procedure. Cite this article: Bone Jt Open 2023;4(11):817–824


The Bone & Joint Journal
Vol. 103-B, Issue 11 | Pages 1725 - 1730
1 Nov 2021
Baumber R Gerrand C Cooper M Aston W

Aims. The incidence of bone metastases is between 20% to 75% depending on the type of cancer. As treatment improves, the number of patients who need surgical intervention is increasing. Identifying patients with a shorter life expectancy would allow surgical intervention with more durable reconstructions to be targeted to those most likely to benefit. While previous scoring systems have focused on surgical and oncological factors, there is a need to consider comorbidities and the physiological state of the patient, as these will also affect outcome. The primary aim of this study was to create a scoring system to estimate survival time in patients with bony metastases and to determine which factors may adversely affect this. Methods. This was a retrospective study which included all patients who had presented for surgery with metastatic bone disease. The data collected included patient, surgical, and oncological variables. Univariable and multivariable analysis identified which factors were associated with a survival time of less than six months and less than one year. A model to predict survival based on these factors was developed using Cox regression. Results. A total of 164 patients were included with a median survival time of 1.6 years (interquartile range 0.5 to 3.1) after surgery. On multivariable analysis, a higher American Society of Anesthesiologists grade (p < 0.001), a high white cell count (p = 0.002), hyponatraemia (p = 0.001), a preoperative resting heart rate of > 100 bpm (p = 0.052), and the type of primary cancer (p = 0.026) remained significant predictors of reduced survival time. The predictive model developed showed good discrimination and calibration to predict both six- and 12-month survival in patients with metastatic bone disease. Conclusion. In addition to surgical and oncological factors, the level of comorbidity and physiological state of the patient has a significant impact on survival in patients with metastatic bone disease. These factors should be considered when assessing the appropriateness of surgical intervention. This is the first study to examine other patient factors alongside surgical and oncological data to identify a relationship between these and survival. Cite this article: Bone Joint J 2021;103-B(11):1725–1730


Bone & Joint 360
Vol. 13, Issue 2 | Pages 38 - 41
1 Apr 2024

The April 2024 Oncology Roundup. 360. looks at: Midterm outcomes of total hip arthroplasty after internal hemipelvectomy and iliofemoral arthrodesis; Intraosseous conventional central chondrosarcoma does not metastasize irrespective of grade in pelvis, scapula, and in long bone locations; Oncological and functional outcomes after resection of malignant tumours of the scapula; Reconstruction following oncological iliosacral resection – a comparison of techniques; Does primary tumour resection improve survival for patients with sarcomas of pelvic bones, sacrum, and coccyx who have metastasis at diagnosis?; Older patients with Ewing’s sarcoma: an analysis of the National Cancer Database; Diagnostic challenges in low-grade central osteosarcoma; Effect of radiotherapy on local recurrence, distant metastasis, and overall survival in 1,200 limb soft-tissue sarcoma patients: a retrospective analysis using inverse probability of treatment weighting-adjusted models


Bone & Joint 360
Vol. 13, Issue 3 | Pages 35 - 36
3 Jun 2024

The June 2024 Spine Roundup. 360. looks at: Intraoperative navigation increases the projected lifetime cancer risk in patients undergoing surgery for adolescent idiopathic scoliosis; Intrawound vancomycin powder reduces delayed deep surgical site infections following posterior spinal fusion for adolescent idiopathic scoliosis; Characterizing negative online reviews of spine surgeons; Proximal junctional failure after surgical instrumentation in adult spinal deformity: biomechanical assessment of proximal instrumentation stiffness; Nutritional supplementation and wound healing: a randomized controlled trial


Bone & Joint Research
Vol. 11, Issue 11 | Pages 803 - 813
1 Nov 2022
Guan X Gong X Jiao ZY Cao HY Liu S Lin C Huang X Lan H Ma L Xu B

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


The Bone & Joint Journal
Vol. 101-B, Issue 3 | Pages 241 - 245
1 Mar 2019
Leaver T Johnson B Lampard J Aarvold A Uglow M

Aims. The aim of this study was to quantify the risk of developing cancer from the exposure to radiation associated with surgery to correct limb deformities in children. Patients and Methods. A total of 35 children were studied. There were 19 girls and 16 boys. Their mean age was 11.9 years (2 to 18) at the time of surgery. Details of the radiological examinations were recorded during gradual correction using a Taylor Spatial Frame. The dose area product for each radiograph was obtained from the Computerised Radiology Information System database. The effective dose in millisieverts (mSv) was calculated using conversion coefficients for the anatomical area. The lifetime risk of developing cancer was calculated using government-approved Health Protection Agency reports, accounting for the age and gender of the child. Results. Correction was undertaken in five femurs, 18 tibiae, and 12 feet. The median duration of treatment was 45 months (11 to 118). The mean effective dose was 0.31 mSv (0.05 to 0.64) for the femur, 0.29 mSv (0.01 to 0.97) for the tibia, and 0.027 mSv (0.001 to 0.161) for the foot. The cumulative exposure gave ‘negligible’ risk in 26 children and ‘minimal’ risk in nine children, according to Public Health England categories. These results are below the mean annual background radiation in the United Kingdom. Conclusion. The lifetime attributable risk of developing cancer from repeated exposure to radiation was negligible or minimal in all children. This is the first study to quantify the exposure to radiation from serial radiographs in children with limb deformities who are treated surgically using circular external fixation, linking this to the risk of developing cancer. Cite this article: Bone Joint J 2019;101-B:241–245


The Bone & Joint Journal
Vol. 104-B, Issue 12 | Pages 1323 - 1328
1 Dec 2022
Cochrane NH Kim B Seyler TM Bolognesi MP Wellman SS Ryan SP

Aims. In the last decade, perioperative advancements have expanded the use of outpatient primary total knee arthroplasty (TKA). Despite this, there remains limited data on expedited discharge after revision TKA. This study compared 30-day readmissions and reoperations in patients undergoing revision TKA with a hospital stay greater or less than 24 hours. The authors hypothesized that expedited discharge in select patients would not be associated with increased 30-day readmissions and reoperations. Methods. Aseptic revision TKAs in the National Surgical Quality Improvement Program database were reviewed from 2013 to 2020. TKAs were stratified by length of hospital stay (greater or less than 24 hours). Patient demographic details, medical comorbidities, American Society of Anesthesiologists (ASA) grade, operating time, components revised, 30-day readmissions, and reoperations were compared. Multivariate analysis evaluated predictors of discharge prior to 24 hours, 30-day readmission, and reoperation. Results. Of 21,610 aseptic revision TKAs evaluated, 530 were discharged within 24 hours. Short-stay patients were younger (63.1 years (49 to 78) vs 65.1 years (18 to 94)), with lower BMI (32.3 kg/m. 2. (17 to 47) vs 33.6 kg/m. 2. (19 to 54) and lower ASA grades. Diabetes, chronic obstructive pulmonary disease, hypertension, and cancer were all associated with a hospital stay over 24 hours. Single component revisions (56.8% (n = 301) vs 32.4% (n = 6,823)), and shorter mean operating time (89.7 minutes (25 to 275) vs 130.2 minutes (30 to 517)) were associated with accelerated discharge. Accelerated discharge was not associated with 30-day readmission and reoperation. Conclusion. Accelerated discharge after revision TKA did not increase short-term complications, readmissions, or reoperations. Further efforts to decrease hospital stays in this setting should be evaluated. Cite this article: Bone Joint J 2022;104-B(12):1323–1328


The Bone & Joint Journal
Vol. 105-B, Issue 8 | Pages 888 - 894
1 Aug 2023
Murray J Jeyapalan R Davies M Sheehan C Petrie M Harrison T

Aims. Total femoral arthroplasty (TFA) is a rare procedure used in cases of significant femoral bone loss, commonly from cancer, infection, and trauma. Low patient numbers have resulted in limited published work on long-term outcomes, and even less regarding TFA undertaken for non-oncological indications. The aim of this study was to evaluate the long-term clinical outcomes of all TFAs in our unit. Methods. Data were collected retrospectively from a large tertiary referral revision arthroplasty unit’s database. Inclusion criteria included all patients who underwent TFA in our unit. Preoperative demographics, operative factors, and short- and long-term outcomes were collected for analysis. Outcome was defined using the Musculoskeletal Infection Society (MSIS) outcome reporting tool. Results. Overall, 38 TFAs were identified. The mean age was 73 years (42 to 80). All patients underwent TFA for non-oncological indications, most commonly as a consequence of infection (53%) and periprosthetic fracture (26%). The mean follow-up time was ten years (0 to 26); 63% of TFAs were considered a success based upon the MSIS outcome reporting tool. The mean time between TFA and death was 8.5 years (0.2 to 19.2), with two patients dying within one year of surgery. Within the cohort, 66% suffered at least one complication, dislocation being most common (37%); 55% of the total cohort required at least one subsequent operation. In total, 70% of TFAs undertaken for infection were considered infection-free at time of final follow-up. The percentage of mobile patients improved from 52% to 65% between pre- and postoperation, with all patients being able to at least transfer from bed to chair at time of final review. Conclusion. This study is the largest in the UK assessing the use of TFA in patients with bone loss secondary to non-oncological conditions. It demonstrates that TFA has a significant complication profile, however it is favourable in terms of mortality and rehabilitation when compared to amputation and disarticulation. Cite this article: Bone Joint J 2023;105-B(8):888–894



Bone & Joint Open
Vol. 3, Issue 12 | Pages 924 - 932
23 Dec 2022
Bourget-Murray J Horton I Morris J Bureau A Garceau S Abdelbary H Grammatopoulos G

Aims. The aims of this study were to determine the incidence and factors for developing periprosthetic joint infection (PJI) following hemiarthroplasty (HA) for hip fracture, and to evaluate treatment outcome and identify factors associated with treatment outcome. Methods. A retrospective review was performed of consecutive patients treated for HA PJI at a tertiary referral centre with a mean 4.5 years’ follow-up (1.6 weeks to 12.9 years). Surgeries performed included debridement, antibiotics, and implant retention (DAIR) and single-stage revision. The effect of different factors on developing infection and treatment outcome was determined. Results. A total of 1,984 HAs were performed during the study period, and 44 sustained a PJI (2.2%). Multiple logistic regression analysis revealed that a higher CCI score (odds ratio (OR) 1.56 (95% confidence interval (CI) 1.117 to 2.187); p = 0.003), peripheral vascular disease (OR 11.34 (95% CI 1.897 to 67.810); p = 0.008), cerebrovascular disease (OR 65.32 (95% CI 22.783 to 187.278); p < 0.001), diabetes (OR 4.82 (95% CI 1.903 to 12.218); p < 0.001), moderate-to-severe renal disease (OR 5.84 (95% CI 1.116 to 30.589); p = 0.037), cancer without metastasis (OR 6.42 (95% CI 1.643 to 25.006); p = 0.007), and metastatic solid tumour (OR 15.64 (95% CI 1.499 to 163.087); p = 0.022) were associated with increasing PJI risk. Upon final follow-up, 17 patients (38.6%) failed initial treatment and required further surgery for HA PJI. One-year mortality was 22.7%. Factors associated with treatment outcome included lower preoperative Hgb level (97.9 g/l (SD 11.4) vs 107.0 g/l (SD 16.1); p = 0.009), elevated CRP level (99.1 mg/l (SD 63.4) vs 56.6 mg/l (SD 47.1); p = 0.030), and type of surgery. There was lower chance of success with DAIR (42.3%) compared to revision HA (66.7%) or revision with conversion to total hip arthroplasty (100%). Early-onset PJI (≤ six weeks) was associated with a higher likelihood of treatment failure (OR 3.5 (95% CI 1.2 to 10.6); p = 0.007) along with patients treated by a non-arthroplasty surgeon (OR 2.5 (95% CI 1.2 to 5.3); p = 0.014). Conclusion. HA PJI initially treated with DAIR is associated with poor chances of success and its value is limited. We strongly recommend consideration of a single-stage revision arthroplasty with cemented components. Cite this article: Bone Jt Open 2022;3(12):924–932



The Bone & Joint Journal
Vol. 100-B, Issue 12 | Pages 1647 - 1654
1 Dec 2018
Shepherd KL Cool P Cribb G

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


Bone & Joint Research
Vol. 11, Issue 5 | Pages 304 - 316
17 May 2022
Kim MH Choi LY Chung JY Kim E Yang WM

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. Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. Methods. We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI. Results. Patients in whom the time to treatment initiation was prolonged had poorer overall survival than those with a TTI of 0 to 30 days. These were: 31 to 60 days (hazard ratio (HR) 1.08, p = 0.011); 61 to 90 days (HR 1.11, p = 0.044); and 91 days (HR 1.22; p = 0.003). The restricted cubic spline showed that the hazard ratio increased substantially with a TTI longer than 50 days. Non-academic centres (vs academic centres; IRR ranging from 0.64 to 0.86; p < 0.001) had a shorter TTI. Those insured by Medicaid (vs private insurance; IRR 1.34), were uninsured (vs private insurance; IRR 1.17), or underwent a transition in care (IRR 1.62) had a longer TTI. Conclusion. A time to treatment initiation of more than 30 days after diagnosis was independently associated with poorer survival. The hazard ratio showed linear increase, especially if the TTI was more than 50 days. We recommend starting treatment within 30 days of diagnosis to achieve the highest likelihood of cure for localized high-grade soft-tissue sarcomas in the limbs and trunk, even when a patient needs to be referred to a specialist centre. Cite this article: Bone Joint J 2021;103-B(6):1142–1149


The Bone & Joint Journal
Vol. 103-B, Issue 4 | Pages 739 - 745
1 Apr 2021
Mehta JS Hodgson K Yiping L Kho JSB Thimmaiah R Topiwala U Sawlani V Botchu R

Aims. To benchmark the radiation dose to patients during the course of treatment for a spinal deformity. Methods. Our radiation dose database identified 25,745 exposures of 6,017 children (under 18 years of age) and adults treated for a spinal deformity between 1 January 2008 and 31 December 2016. Patients were divided into surgical (974 patients) and non-surgical (5,043 patients) cohorts. We documented the number and doses of ionizing radiation imaging events (radiographs, CT scans, or intraoperative fluoroscopy) for each patient. All the doses for plain radiographs, CT scans, and intraoperative fluoroscopy were combined into a single effective dose by a medical physicist (milliSivert (mSv)). Results. There were more ionizing radiation-based imaging events and higher radiation dose exposures in the surgical group than in the non-surgical group (p < 0.001). The difference in effective dose for children between the surgical and non-surgical groups was statistically significant, the surgical group being significantly higher (p < 0.001). This led to a higher estimated risk of cancer induction for the surgical group (1:222 surgical vs 1:1,418 non-surgical). However, the dose difference for adults was not statistically different between the surgical and non-surgical groups. In all cases the effective dose received by all cohorts was significantly higher than that from exposure to natural background radiation. Conclusion. The treatment of spinal deformity is radiation-heavy. The dose exposure is several times higher when surgical treatment is undertaken. Clinicians should be aware of this and review their practices in order to reduce the radiation dose where possible. Cite this article: Bone Joint J 2021;103-B(4):1–7


Bone & Joint Open
Vol. 2, Issue 2 | Pages 79 - 85
15 Feb 2021
Downie S Stillie A Moran M Sudlow C Simpson AHRW

Aims. Surgery is often indicated in patients with metastatic bone disease (MBD) to improve pain and maximize function. Few studies are available which report on clinically meaningful outcomes such as quality of life, function, and pain relief after surgery for MBD. This is the published protocol for the Bone Metastasis Audit — Patient Reported Outcomes (BoMA-PRO) multicentre MBD study. The primary objective is to ascertain patient-reported quality of life at three to 24 months post-surgery for MBD. Methods. This will be a prospective, longitudinal study across six UK orthopaedic centres powered to identify the influence of ten patient variables on quality of life at three months after surgery for MBD. Adult patients managed for bone metastases will be screened by their treating consultant and posted out participant materials. If they opt in to participate, they will receive questionnaire packs at regular intervals from three to 24 months post-surgery and their electronic records will be screened until death or five years from recruitment. The primary outcome is quality of life as measured by the European Organisation for Research and the Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ) C30 questionnaire. The protocol has been approved by the Newcastle & North Tyneside 2 Research Ethics Committee (REC ref 19/NE/0303) and the study is funded by the Royal College of Physicians and Surgeons of Glasgow (RCPSG) and the Association for Cancer Surgery (BASO-ACS). Discussion. This will be the first powered study internationally to investigate patient-reported outcomes after orthopaedic treatment for bone metastases. We will assess quality of life, function, and pain relief at three to 24 months post-surgery and identify which patient variables are significantly associated with a good outcome after MBD treatment. Cite this article: Bone Jt Open 2021;2(2):79–85


Bone & Joint Research
Vol. 10, Issue 4 | Pages 237 - 249
1 Apr 2021
Chen X Chen W Aung ZM Han W Zhang Y Chai G

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. Methods. The function of LY3023414 was explored in the context of osteogenesis (bone formation by osteoblasts) and osteoclastogenesis (osteoclast formation and bone resorption). Murine preosteoblast MC3T3-E1 cell line and murine bone marrow-derived macrophage cells (BMMs) were subjected to different treatments. An MTS cell proliferation assay was used to examine the cytotoxicity. Thereafter, different induction conditions were applied, such as MCSF and RANKL for osteoclastogenesis and osteogenic media for osteogenesis. Specific staining, a bone resorption assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were subsequently used to evaluate the effect of LY3023414. Moreover, small interfering RNA (siRNA) was applied to knockdown Akt1 or Akt2 for further validation. Lastly, western blot was used to examine the exact mechanism of action. Results. LY3023414 attenuated PI3K/protein kinase B (Akt)/GSK3-dependent activation of β-catenin and nuclear factor-activated T cell 1 (NFATc1) during osteogenesis and osteoclastogenesis, respectively. LY3023414 mainly inhibited osteoclast formation instead of mature osteoclast function. Moreover, it suppressed osteogenesis both in the early stage of differentiation and late stage of calcification. Similarly, gene knockdown of Akt isoforms by siRNA downregulated osteogenic and osteoclastogenic processes, indicating that Akt1 and Akt2 acted synergistically. Conclusion. LY3023414 can suppress osteogenesis and osteoclastogenesis through inhibition of the PI3K/Akt/GSK3 signalling pathway, which highlights the potential benefits and side effects of LY3023414 for future clinical applications. Cite this article: Bone Joint Res 2021;10(4):237–249


The Bone & Joint Journal
Vol. 103-B, Issue 3 | Pages 469 - 478
1 Mar 2021
Garland A Bülow E Lenguerrand E Blom A Wilkinson M Sayers A Rolfson O Hailer NP

Aims. To develop and externally validate a parsimonious statistical prediction model of 90-day mortality after elective total hip arthroplasty (THA), and to provide a web calculator for clinical usage. Methods. We included 53,099 patients with cemented THA due to osteoarthritis from the Swedish Hip Arthroplasty Registry for model derivation and internal validation, as well as 125,428 patients from England and Wales recorded in the National Joint Register for England, Wales, Northern Ireland, the Isle of Man, and the States of Guernsey (NJR) for external model validation. A model was developed using a bootstrap ranking procedure with a least absolute shrinkage and selection operator (LASSO) logistic regression model combined with piecewise linear regression. Discriminative ability was evaluated by the area under the receiver operating characteristic curve (AUC). Calibration belt plots were used to assess model calibration. Results. A main effects model combining age, sex, American Society for Anesthesiologists (ASA) class, the presence of cancer, diseases of the central nervous system, kidney disease, and diagnosed obesity had good discrimination, both internally (AUC = 0.78, 95% confidence interval (CI) 0.75 to 0.81) and externally (AUC = 0.75, 95% CI 0.73 to 0.76). This model was superior to traditional models based on the Charlson (AUC = 0.66, 95% CI 0.62 to 0.70) and Elixhauser (AUC = 0.64, 95% CI 0.59 to 0.68) comorbidity indices. The model was well calibrated for predicted probabilities up to 5%. Conclusion. We developed a parsimonious model that may facilitate individualized risk assessment prior to one of the most common surgical interventions. We have published a web calculator to aid clinical decision-making. Cite this article: Bone Joint J 2021;103-B(3):469–478


Bone & Joint Research
Vol. 9, Issue 11 | Pages 821 - 826
1 Nov 2020
Hagi T Nakamura T Kita K Iino T Asanuma K Sudo A

Aims. Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines. Methods. We used the 143B, HOS, and Saos-2 human OS cell lines. We first analyzed the IL-6 gene expression and IL-6Rα protein expression in OS cells using reverse transcription real time quantitative-polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. We also assessed the effect of tocilizumab on OS cells using proliferation and invasion assay. Results. The OS cell lines 143B, HOS, and Saos-2 expressed IL-6R. Recombinant human IL-6 treatment increased proliferation of 143B and HOS cells. Tocilizumab treatment decreased proliferation and invasion of 143B, HOS, and Saos-2. Conclusion. In conclusion, we confirmed the production of IL-6 and the expression of IL-6R in OS cells and demonstrated that tocilizumab inhibits proliferation and invasion in OS cells. Cite this article: Bone Joint Res 2020;9(11):821–826






The Bone & Joint Journal
Vol. 102-B, Issue 12 | Pages 1709 - 1716
1 Dec 2020
Kanda Y Kakutani K Sakai Y Yurube T Miyazaki S Takada T Hoshino Y Kuroda R

Aims. With recent progress in cancer treatment, the number of advanced-age patients with spinal metastases has been increasing. It is important to clarify the influence of advanced age on outcomes following surgery for spinal metastases, especially with a focus on subjective health state values. Methods. We prospectively analyzed 101 patients with spinal metastases who underwent palliative surgery from 2013 to 2016. These patients were divided into two groups based on age (< 70 years and ≥ 70 years). The Eastern Cooperative Oncology Group (ECOG) performance status (PS), Barthel index (BI), and EuroQol-5 dimension (EQ-5D) score were assessed at study enrolment and at one, three, and six months after surgery. The survival times and complications were also collected. Results. In total, 65 patients were aged < 70 years (mean 59.6 years; 32 to 69) and 36 patients were aged ≥ 70 years (mean 75.9 years; 70 to 90). In both groups, the PS improved from PS3 to PS1 by spine surgery, the mean BI improved from < 60 to > 80 points, and the mean EQ-5D score improved from 0.0 to > 0.7 points. However, no significant differences were found in the improvement rates and values of the PS, BI, and EQ-5D score at any time points between the two groups. The PS, BI, and EQ-5D score improved throughout the follow-up period in approximately 90% of patients in each group. However, the improved PS, BI, and EQ-5D scores subsequently deteriorated in some patients, and the redeterioration rate of the EQ-5D was significantly higher in patients aged ≥ 70 than < 70 years (p = 0.027). Conclusion. Palliative surgery for spinal metastases improved the PS, activities of daily living, and quality of life, regardless of age. However, clinicians should be aware of the higher risk of redeterioration of the quality of life in advanced-age patients. Cite this article: Bone Joint J 2020;102-B(12):1709–1716



Bone & Joint Research
Vol. 6, Issue 3 | Pages 186 - 193
1 Mar 2017
Choi YJ Lee YS Lee HW Shim DM Seo SW

Objectives. Eukaryotic translation initiation factor 3 (eIF3) is a multi-subunit complex that plays a critical role in translation initiation. Expression levels of eIF3 subunits are elevated or decreased in various cancers, suggesting a role for eIF3 in tumorigenesis. Recent studies have shown that the expression of the eIF3b subunit is elevated in bladder and prostate cancer, and eIF3b silencing inhibited glioblastoma growth and induced cellular apoptosis. In this study, we investigated the role of eIF3b in the survival of osteosarcoma cells. Methods. To investigate the effect of eIF3b on cell viability and apoptosis in osteosarcoma cells, we first examined the silencing effect of eIF3b in U2OS cells. Cell viability and apoptosis were examined by the Cell Counting Kit-8 (CCK-8) assay and Western blot, respectively. We also performed gene profiling to identify genes affected by eIF3b silencing. Finally, the effect of eIF3b on cell viability and apoptosis was confirmed in multiple osteosarcoma cell lines. Results. eIF3b silencing decreased cell viability and induced apoptosis in U2OS cells, and by using gene profiling we discovered that eIF3b silencing also resulted in the upregulation of tumour necrosis factor receptor superfamily member 21 (TNFRSF21). We found that TNFRSF21 overexpression induced cell death in U2OS cells, and we confirmed that eIF3b silencing completely suppressed cell growth in multiple osteosarcoma cell lines. However, eIF3b silencing failed to suppress cell growth completely in normal fibroblast cells. Conclusion. Our data led us to conclude that eIF3b may be required for osteosarcoma cell proliferation by regulating TNFRSF21 expression. Cite this article: Y. J. Choi, Y. S. Lee, H. W. Lee, D. M. Shim, S. W. Seo. Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells. Bone Joint Res 2017;6:186–193. DOI: 10.1302/2046-3758.63.BJR-2016-0151.R2


The Bone & Joint Journal
Vol. 102-B, Issue 3 | Pages 285 - 292
1 Mar 2020
Tanaka A Katagiri H Murata H Wasa J Miyagi M Honda Y Takahashi M

Aims. The aim of this study is to evaluate the clinical results of operative intervention for femoral metastases which were selected based on expected survival and to discuss appropriate surgical strategies. Methods. From 2002 to 2017, 148 consecutive patients undergoing surgery for femoral metastasis were included in this study. Prognostic risk assessments were performed according to the Katagiri and revised Katagiri scoring system. In general, the low-risk group underwent resection and reconstruction with endoprosthetic replacement (EPR), while the high-risk group underwent internal fixation (IF) and radiation therapy. For the intermediate-risk group, the operative choice depended on the patient’s condition, degree of bone destruction, and radio-sensitivity. Overall survival, local failure, walking ability, and systemic complications were evaluated. Results. A total of 83 patients underwent EPR (low-risk, 23%; intermediate-risk, 60%; high-risk, 17%) and 65 patients underwent IF (low-risk, 0%; intermediate-risk, 32%; high-risk, 68%). The one-year survival rate was 71% for EPR and 15% for IF (p < 0.001). The one-year local failure-free survival was 93% for EPR and 67% for IF, and the two-year and five-year local failure-free survival for EPR were both 88% (p = 0.016). Although the ambulatory rate was 99% for EPR and 60% for IF, the median time to ambulation was shorter in the IF (EPR, 28 days, interquartile range (IQR) 25 to 35; IF, 23 days, IQR 18 to 28; p < 0.001) The cause of non ambulation was mainly due to progression of cancer (89%). The rate of systemic complications was comparable between the two groups (EPR, 18%; IF, 22%; p = 0.598). Conclusion. Selective use of EPR where survival is expected to be good offers correspondingly good long-term results. IF is less invasive with shorter treatment period, which is beneficial for patients with short-term expected survival. Prognosis is an important indicator in selecting operative procedures for femoral metastasis. Cite this article: Bone Joint J 2020;102-B(3):285–292


The Bone & Joint Journal
Vol. 102-B, Issue 1 | Pages 72 - 81
1 Jan 2020
Downie S Lai FY Joss J Adamson D Jariwala AC

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


Bone & Joint Research
Vol. 9, Issue 7 | Pages 333 - 340
1 Jul 2020
Mumith A Coathup M Edwards TC Gikas P Aston W Blunn G

Aims. Limb salvage in bone tumour patients replaces the bone with massive segmental prostheses where achieving bone integration at the shoulder of the implant through extracortical bone growth has been shown to prevent loosening. This study investigates the effect of multidrug chemotherapy on extracortical bone growth and early radiological signs of aseptic loosening in patients with massive distal femoral prostheses. Methods. A retrospective radiological analysis was performed on adult patients with distal femoral arthroplasties. In all, 16 patients were included in the chemotherapy group with 18 patients in the non-chemotherapy control group. Annual radiographs were analyzed for three years postoperatively. Dimensions of the bony pedicle, osseointegration of the hydroxyapatite (HA) collar surface, bone resorption at the implant shoulder, and radiolucent line (RLL) formation around the cemented component were analyzed. Results. A greater RLL score (p = 0.041) was observed at three years postoperatively, with those receiving chemotherapy showing greater radiological loosening compared with those not receiving chemotherapy. Chemotherapy patients experience osteolysis at the shoulder of the ingrowth collar over time (p < 0.001) compared with non-chemotherapy patients where osteolysis was not observed. A greater median percentage integration of the collar surface was observed in the non-chemotherapy group (8.6%, interquartile range (IQR) 0.0% to 37.9%; p = 0.021) at three years. Bone growth around the collar was observed in both groups, and no statistical difference in amount of extracortical bony bridging was seen. Conclusion. Multidrug chemotherapy affects the osseointegration of ingrowth collars and accelerates signs of radiological loosening. This may increase the risk of aseptic loosening in patients with massive segmental implants used to treat bone cancer. Cite this article: Bone Joint Res 2020;9(7):333–340


The Bone & Joint Journal
Vol. 97-B, Issue 9 | Pages 1284 - 1290
1 Sep 2015
Furtado S Grimer RJ Cool P Murray SA Briggs T Fulton J Grant K Gerrand CH

Patients who have limb amputation for musculoskeletal tumours are a rare group of cancer survivors. This was a prospective cross-sectional survey of patients from five specialist centres for sarcoma surgery in England. Physical function, pain and quality of life (QOL) outcomes were collected after lower extremity amputation for bone or soft-tissue tumours to evaluate the survivorship experience and inform service provision. Of 250 patients, 105 (42%) responded between September 2012 and June 2013. From these, completed questionnaires were received from 100 patients with a mean age of 53.6 years (19 to 91). In total 60 (62%) were male and 37 (38%) were female (three not specified). The diagnosis was primary bone sarcoma in 63 and soft-tissue tumour in 37. A total of 20 tumours were located in the hip or pelvis, 31 above the knee, 32 between the knee and ankle and 17 in the ankle or foot. In total 22 had hemipelvectomy, nine hip disarticulation, 35 transfemoral amputation, one knee disarticulation, 30 transtibial amputation, two toe amputations and one rotationplasty. The Toronto Extremity Salvage Score (TESS) differed by amputation level, with poorer scores at higher levels (p < 0.001). Many reported significant pain. In addition, TESS was negatively associated with increasing age, and pain interference scores. QOL for Cancer Survivors was significantly correlated with TESS (p < 0.001). This relationship appeared driven by pain interference scores. . This unprecedented national survey confirms amputation level is linked to physical function, but not QOL or pain measures. Pain and physical function significantly impact on QOL. These results are helpful in managing the expectations of patients about treatment and addressing their complex needs. Cite this article: Bone Joint J 2015;97-B:1284–90


The Bone & Joint Journal
Vol. 101-B, Issue 6 | Pages 691 - 694
1 Jun 2019
Tonge XN Widnall JC Jackson G Platt S

Aims. To our knowledge, there is currently no information available about the rate of venous thromboembolism (VTE) or recommendations regarding chemoprophylaxis for patients whose lower limb is immobilized in a plaster cast. We report a retrospective case series assessing the rate of symptomatic VTE in patients treated with a lower limb cast. Given the complex, heterogeneous nature of this group of patients, with many risk factors for VTE, we hypothesized that the rate of VTE would be higher than in the general population. Patients and Methods. Patients treated with a lower limb cast between 2006 and 2018 were identified using plaster room records. Their electronic records and radiological reports were reviewed for details about their cast, past medical history, and any VTE recorded in our hospital within a year of casting. Results. There were 136 episodes of casting in 100 patients. The mean age was 55 years (22 to 91). The mean time in a cast was 45 days (five days to eight months). A total of 76 patients had neuropathy secondary to diabetes. No patient received chemical thromboprophylaxis while in a cast. One VTE (0.7% of casting episodes) was documented. This was confirmed by Doppler scan nine days after removing the cast. Conclusion. The frequency of VTE was higher than that of the general population (0.05%); this is most likely attributable to our patients’ apparent increase in VTE risk as suggested by The National Institute for Health and Care Excellence (NICE). These findings suggest that thromboprophylaxis is not routinely indicated in patients who undergo immobilization of the lower limb in a cast, although the risks of VTE should be assessed. While the cast itself does not pose an increased risk, other pathologies, such as active cancer, mean that each individual case needs to be considered on their merit. Cite this article: Bone Joint J 2019;101-B:691–694




The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 1 | Pages 47 - 51
1 Jan 2011
Hetsroni I Lyman S Do H Mann G Marx RG

Pulmonary embolism is a serious complication after arthroscopy of the knee, about which there is limited information. We have identified the incidence and risk factors for symptomatic pulmonary embolism after arthroscopic procedures on outpatients. The New York State Department of Health Statewide Planning and Research Cooperative System database was used to review arthroscopic procedures of the knee performed on outpatients between 1997 and 2006, and identify those admitted within 90 days of surgery with an associated diagnosis of pulmonary embolism. Potential risk factors included age, gender, complexity of surgery, operating time defined as the total time that the patient was actually in the operating room, history of cancer, comorbidities, and the type of anaesthesia. We identified 374 033 patients who underwent 418 323 outpatient arthroscopies of the knee. There were 117 events of pulmonary embolism (2.8 cases for every 10 000 arthroscopies). Logistic regression analysis showed that age and operating time had significant dose-response increases in risk (p < 0.001) for a subsequent admission with a pulmonary embolism. Female gender was associated with a 1.5-fold increase in risk (p = 0.03), and a history of cancer with a threefold increase (p = 0.05). These risk factors can be used when obtaining informed consent before surgery, to elevate the level of clinical suspicion of pulmonary embolism in patients at risk, and to establish a rationale for prospective studies to test the clinical benefit of thromboprophylaxis in high-risk patients


Bone & Joint Research
Vol. 12, Issue 6 | Pages 375 - 386
12 Jun 2023
Li Z

Aims

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.

Methods

Using quantitative real-time polymerase chain reaction (qRT-PCR), osteogenesis-related genes (alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2)), PCBP1-AS1, microRNA (miR)-126-5p, group I Pak family member p21-activated kinase 2 (PAK2), and their relative expression levels were determined. Western blotting was used to examine the expression of PAK2 protein. Cell Counting Kit-8 (CCK-8) assay was used to measure cell proliferation. To examine the osteogenic differentiation, Alizarin red along with ALP staining was used. RNA immunoprecipitation assay and bioinformatics analysis, as well as a dual-luciferase reporter, were used to study the association between PCBP1-AS1, PAK2, and miR-126-5p.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 157 - 168
4 Apr 2024
Lin M Chen G Yu H Hsu P Lee C Cheng C Wu S Pan B Su B

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.


The Bone & Joint Journal
Vol. 105-B, Issue 6 | Pages 702 - 710
1 Jun 2023
Yeramosu T Ahmad W Bashir A Wait J Bassett J Domson G

Aims

The aim of this study was to identify factors associated with five-year cancer-related mortality in patients with limb and trunk soft-tissue sarcoma (STS) and develop and validate machine learning algorithms in order to predict five-year cancer-related mortality in these patients.

Methods

Demographic, clinicopathological, and treatment variables of limb and trunk STS patients in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2004 to 2017 were analyzed. Multivariable logistic regression was used to determine factors significantly associated with five-year cancer-related mortality. Various machine learning models were developed and compared using area under the curve (AUC), calibration, and decision curve analysis. The model that performed best on the SEER testing data was further assessed to determine the variables most important in its predictive capacity. This model was externally validated using our institutional dataset.


The Bone & Joint Journal
Vol. 104-B, Issue 12 | Pages 1284 - 1291
1 Dec 2022
Rose PS

Tumours of the sacrum are difficult to manage. The sacrum provides the structural connection between the torso and lower half of the body and is subject to both axial and rotational forces. Thus, tumours or their treatment can compromise the stability of the spinopelvic junction. Additionally, nerves responsible for lower limb motor groups as well as bowel, bladder, and sexual function traverse or abut the sacrum. Preservation or sacrifice of these nerves in the treatment of sacral tumours has profound implications on the function and quality of life of the patient. This annotation will discuss current treatment protocols for sacral tumours.

Cite this article: Bone Joint J 2022;104-B(12):1284–1291.


Bone & Joint 360
Vol. 4, Issue 4 | Pages 30 - 31
1 Aug 2015

The August 2015 Oncology Roundup. 360 . looks at: Glasgow prognostic score in soft-tissue sarcoma; Denosumab in giant cell tumour; Timing, complications and radiotherapy; Pigmented villonodular synovitis and arthroscopy; PATHFx: estimating survival in pathological cancer; Prosthetic lengthening of short stumps; Chondrosarcoma and pathological fracture


Bone & Joint Open
Vol. 4, Issue 6 | Pages 424 - 431
5 Jun 2023
Christ AB Piple AS Gettleman BS Duong A Chen M Wang JC Heckmann ND Menendez L

Aims

The modern prevalence of primary tumours causing metastatic bone disease is ill-defined in the oncological literature. Therefore, the purpose of this study is to identify the prevalence of primary tumours in the setting of metastatic bone disease, as well as reported rates of pathological fracture, postoperative complications, 90-day mortality, and 360-day mortality for each primary tumour subtype.

Methods

The Premier Healthcare Database was queried to identify all patients who were diagnosed with metastatic bone disease from January 2015 to December 2020. The prevalence of all primary tumour subtypes was tabulated. Rates of long bone pathological fracture, 90-day mortality, and 360-day mortality following surgical treatment of pathological fracture were assessed for each primary tumour subtype. Patient characteristics and postoperative outcomes were analyzed based upon whether patients had impending fractures treated prophylactically versus treated completed fractures.


Bone & Joint Research
Vol. 11, Issue 9 | Pages 639 - 651
7 Sep 2022
Zou Y Zhang X Liang J Peng L Qin J Zhou F Liu T Dai L

Aims

To explore the synovial expression of mucin 1 (MUC1) and its role in rheumatoid arthritis (RA), as well as the possible downstream mechanisms.

Methods

Patients with qualified synovium samples were recruited from a RA cohort. Synovium from patients diagnosed as non-inflammatory orthopaedic arthropathies was obtained as control. The expression and localization of MUC1 in synovium and fibroblast-like synoviocytes were assessed by immunohistochemistry and immunofluorescence. Small interfering RNA and MUC1 inhibitor GO-203 were adopted for inhibition of MUC1. Lysophosphatidic acid (LPA) was used as an activator of Rho-associated pathway. Expression of inflammatory cytokines, cell migration, and invasion were evaluated using quantitative real-time polymerase chain reaction (PCR) and Transwell chamber assay.


Bone & Joint Open
Vol. 3, Issue 8 | Pages 648 - 655
1 Aug 2022
Yeung CM Bhashyam AR Groot OQ Merchan N Newman ET Raskin KA Lozano-Calderón SA

Aims

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.

Methods

This single tertiary-institutional, retrospectively matched case-control study included 72 patients who underwent prophylactic or therapeutic fixation for pathological fracture of the humerus, femur, or tibia with either a titanium (control group, n = 36) or carbon fibre (case group, n = 36) intramedullary nail between 2016 to 2020. Patients were excluded if intramedullary fixation was combined with any other surgical procedure/fixation method. Outcomes included operating time, blood loss, fluoroscopic time, and complications. Fisher’s exact test and Mann-Whitney U test were used for categorical and continuous outcomes, respectively.


The Bone & Joint Journal
Vol. 105-B, Issue 10 | Pages 1115 - 1122
1 Oct 2023
Archer JE Chauhan GS Dewan V Osman K Thomson C Nandra RS Ashford RU Cool P Stevenson J

Aims

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.

Methods

A prospective, multicentre, national collaborative audit was designed and delivered by a trainee-led collaborative group. Data were collected over three months (1 April 2021 to 30 June 2021) for all patients presenting with MBD. A data collection tool allowed investigators at each hospital to compare practice against guidelines. Data were collated and analyzed centrally to quantify compliance from 84 hospitals in the UK for a total of 1,137 patients who were eligible for inclusion.


Bone & Joint Open
Vol. 4, Issue 3 | Pages 168 - 181
14 Mar 2023
Dijkstra H Oosterhoff JHF van de Kuit A IJpma FFA Schwab JH Poolman RW Sprague S Bzovsky S Bhandari M Swiontkowski M Schemitsch EH Doornberg JN Hendrickx LAM

Aims

To develop prediction models using machine-learning (ML) algorithms for 90-day and one-year mortality prediction in femoral neck fracture (FNF) patients aged 50 years or older based on the Hip fracture Evaluation with Alternatives of Total Hip arthroplasty versus Hemiarthroplasty (HEALTH) and Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trials.

Methods

This study included 2,388 patients from the HEALTH and FAITH trials, with 90-day and one-year mortality proportions of 3.0% (71/2,388) and 6.4% (153/2,388), respectively. The mean age was 75.9 years (SD 10.8) and 65.9% of patients (1,574/2,388) were female. The algorithms included patient and injury characteristics. Six algorithms were developed, internally validated and evaluated across discrimination (c-statistic; discriminative ability between those with risk of mortality and those without), calibration (observed outcome compared to the predicted probability), and the Brier score (composite of discrimination and calibration).


Bone & Joint 360
Vol. 2, Issue 6 | Pages 2 - 8
1 Dec 2013
Jones R Wood D

This article provides an overview of the role of genomics in sarcomas and describes how new methods of analysis and comparative screening have provided the potential to progress understanding and treatment of sarcoma. This article reviews genomic techniques, the evolution of the use of genomics in cancer, the current state of genomic analysis, and also provides an overview of the medical, social and economic implications of recent genomic advances


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 271 - 277
1 Feb 2016
Sørensen MS Gerds TA Hindsø K Petersen MM

Aims. The purpose of this study was to develop a prognostic model for predicting survival of patients undergoing surgery owing to metastatic bone disease (MBD) in the appendicular skeleton. Methods. We included a historical cohort of 130 consecutive patients (mean age 64 years, 30 to 85; 76 females/54 males) who underwent joint arthroplasty surgery (140 procedures) owing to MBD in the appendicular skeleton during the period between January 2003 and December 2008. Primary cancer, pre-operative haemoglobin, fracture versus impending fracture, Karnofsky score, visceral metastases, multiple bony metastases and American Society of Anaesthesiologist’s score were included into a series of logistic regression models. The outcome was the survival status at three, six and 12 months respectively. Results were internally validated based on 1000 cross-validations and reported as time-dependent area under the receiver-operating characteristic curves (AUC) for predictions of outcome. . Results. The predictive scores obtained showed AUC values of 79.1% (95% confidence intervals (CI) 65.6 to 89.6), 80.9% (95% CI 70.3 to 90.84) and 85.1% (95% CI 73.5 to 93.9) at three, six and 12 months. . Discussion. In conclusion, we have presented and internally validated a model for predicting survival after surgery owing to MBD in the appendicular skeleton. The model is the first, to our knowledge, built solely on material from patients who only had surgery in the appendicular skeleton. Take home message: Applying this prognostic model will help determine whether the patients’ anticipated survival makes it reasonable to subject them to extensive reconstructive surgery for which there may be an extended period of rehabilitation. Cite this article: Bone Joint J 2016;98-B:271–7


Bone & Joint 360
Vol. 13, Issue 1 | Pages 35 - 38
1 Feb 2024

The February 2024 Oncology Roundup360 looks at: Does primary tumour resection improve survival for patients with sarcomas of the pelvis with metastasis at diagnosis?; Proximal femur replacements for an oncologic indication offer a durable endoprosthetic reconstruction option: a 40-year experience; The importance of awaiting biopsy results in solitary pathological proximal femoral fractures: do we need to biopsy solitary pathological fractures?; Effect of radiotherapy on local recurrence, distant metastasis, and overall survival in 1,200 extremity soft-tissue sarcoma patients; What to choose in bone tumour resections? Patient-specific instrumentation versus surgical navigation; Optimal timing of re-excision in synovial sarcoma patients: immediate intervention versus waiting for local recurrence; Survival differences of patients with resected extraskeletal osteosarcoma receiving two different (neo) adjuvant chemotherapy regimens; Solitary versus multiple bone metastases in the appendicular skeleton: should the surgical treatment be different?.


The Bone & Joint Journal
Vol. 105-B, Issue 11 | Pages 1216 - 1225
1 Nov 2023
Fujiwara T Kunisada T Nakata E Mitsuhashi T Ozaki T Kawai A

Aims

Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment.

Methods

The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan.


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 266 - 270
1 Feb 2016
Stevenson JD McNair M Cribb GL Cool WP

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


Bone & Joint Research
Vol. 7, Issue 2 | Pages 179 - 186
1 Feb 2018
Wu T Zhang J Wang B Sun Y Liu Y Li G

Objectives. As one of the heat-stable enterotoxins, Staphylococcal enterotoxin C2 (SEC2) is synthesized by Staphylococcus aureus, which has been proved to inhibit the growth of tumour cells, and is used as an antitumour agent in cancer immunotherapy. Although SEC2 has been reported to promote osteogenic differentiation of human mesenchymal stem cells (MSCs), the in vivo function of SCE2 in animal model remains elusive. The aim of this study was to further elucidate the in vivo effect of SCE2 on fracture healing. Materials and Methods. Rat MSCs were used to test the effects of SEC2 on their proliferation and osteogenic differentiation potentials. A rat femoral fracture model was used to examine the effect of local administration of SEC2 on fracture healing using radiographic analyses, micro-CT analyses, biomechanical testing, and histological analyses. Results. While SEC2 was found to have no effect on rat MSCs proliferation, it promoted the osteoblast differentiation of rat MSCs. In the rat femoral fracture model, the local administration of SEC2 accelerated fracture healing by increasing fracture callus volumes, bone volume over total volume (BV/TV), and biomechanical recovery. The SEC2 treatment group has superior histological appearance compared with the control group. Conclusion. These data suggest that local administration of SEC2 may be a novel therapeutic approach to enhancing bone repair such as fracture healing. Cite this article: T. Wu, J. Zhang, B. Wang, Y. Sun, Y. Liu, G. Li. Staphylococcal enterotoxin C2 promotes osteogenesis of mesenchymal stem cells and accelerates fracture healing. Bone Joint Res 2018;7:179–186. DOI: 10.1302/2046-3758.72.BJR-2017-0229.R1


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 160 - 165
1 Feb 2016
Farrier AJ C. Sanchez Franco L Shoaib A Gulati V Johnson N Uzoigwe CE Choudhury MZ

The ageing population and an increase in both the incidence and prevalence of cancer pose a healthcare challenge, some of which is borne by the orthopaedic community in the form of osteoporotic fractures and metastatic bone disease. In recent years there has been an increasing understanding of the pathways involved in bone metabolism relevant to osteoporosis and metastases in bone. Newer therapies may aid the management of these problems. One group of drugs, the antibody mediated anti-resorptive therapies (AMARTs) use antibodies to block bone resorption pathways. This review seeks to present a synopsis of the guidelines, pharmacology and potential pathophysiology of AMARTs and other new anti-resorptive drugs. . We evaluate the literature relating to AMARTs and new anti-resorptives with special attention on those approved for use in clinical practice. Denosumab, a monoclonal antibody against Receptor Activator for Nuclear Factor Kappa-B Ligand. It is the first AMART approved by the National Institute for Health and Clinical Excellence and the US Food and Drug Administration. Other novel anti-resorptives awaiting approval for clinical use include Odanacatib. Denosumab is indicated for the treatment of osteoporosis and prevention of the complications of bone metastases. Recent evidence suggests, however, that denosumab may have an adverse event profile similar to bisphosphonates, including atypical femoral fractures. It is, therefore, essential that orthopaedic surgeons are conversant with these medications and their safe usage. . Take home message: Denosumab has important orthopaedic indications and has been shown to significantly reduce patient morbidity in osteoporosis and metastatic bone disease. Cite this article: Bone Joint J 2016;98-B:160–5


Bone & Joint Open
Vol. 4, Issue 10 | Pages 766 - 775
13 Oct 2023
Xiang L Singh M McNicoll L Moppett IK

Aims

To identify factors influencing clinicians’ decisions to undertake a nonoperative hip fracture management approach among older people, and to determine whether there is global heterogeneity regarding these factors between clinicians from high-income countries (HIC) and low- and middle-income countries (LMIC).

Methods

A SurveyMonkey questionnaire was electronically distributed to clinicians around the world through the Fragility Fracture Network (FFN)’s Perioperative Special Interest Group and clinicians’ personal networks between 24 May and 25 July 2021. Analyses were performed using Excel and STATA v16.0. Between-group differences were determined using independent-samples t-tests and chi-squared tests.


Bone & Joint 360
Vol. 3, Issue 1 | Pages 32 - 34
1 Feb 2014

The February 2014 Oncology Roundup. 360 . looks at: suspicious lesions; limb salvage in pelvic sarcomas; does infection affect oncological survival?; cancer patient pathways; radiological arthritis with cement augmentation in GCT; and post-chemotherapy increase in tumour volume as a predictor of poor prognosis


Bone & Joint 360
Vol. 11, Issue 6 | Pages 40 - 41
1 Dec 2022

The December 2022 Oncology Roundup360 looks at: Is high-dose radiation therapy associated with early revision with a cemented endoprosthesis?; Neoadjuvant chemotherapy and endoprosthetic reconstruction for lower extremity sarcomas: does timing impact complication rates?; Late amputation after treatment for lower extremity sarcoma; Osteosarcoma prediagnosed as another tumour: a report from the Cooperative Osteosarcoma Study Group; The influence of site on the incidence and diagnosis of solitary central cartilage tumours of the femur: a 21st century perspective.


Bone & Joint 360
Vol. 11, Issue 5 | Pages 37 - 38
1 Oct 2022


Bone & Joint Open
Vol. 4, Issue 6 | Pages 442 - 446
12 Jun 2023
Toda Y Iwata S Kobayashi E Ogura K Osaki S Fukushima S Mawatari M Kawai A

Aims

The risk of postoperative complications after resection of soft-tissue sarcoma in the medial thigh is higher than in other locations. This study investigated whether a vessel sealing system (VSS) could help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh.

Methods

Of 285 patients who underwent wide resection for soft-tissue sarcoma between 2014 and 2021 at our institution, 78 patients with tumours in the medial thigh were extracted from our database. Information on clinicopathological characteristics, preoperative treatment, surgical treatment (use of VSS, blood loss volume, operating time), and postoperative course (complications, postoperative haemoglobin changes, total drainage volume, and drainage and hospitalization durations) were obtained from medical records. We statistically compared clinical outcomes between patients whose surgery did or did not use VSS (VSS and non-VSS groups, respectively).


Bone & Joint Open
Vol. 4, Issue 5 | Pages 338 - 356
10 May 2023
Belt M Robben B Smolders JMH Schreurs BW Hannink G Smulders K

Aims

To map literature on prognostic factors related to outcomes of revision total knee arthroplasty (rTKA), to identify extensively studied factors and to guide future research into what domains need further exploration.

Methods

We performed a systematic literature search in MEDLINE, Embase, and Web of Science. The search string included multiple synonyms of the following keywords: "revision TKA", "outcome" and "prognostic factor". We searched for studies assessing the association between at least one prognostic factor and at least one outcome measure after rTKA surgery. Data on sample size, study design, prognostic factors, outcomes, and the direction of the association was extracted and included in an evidence map.


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.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 594 - 607
17 Aug 2022
Zhou Y Li J Xu F Ji E Wang C Pan Z

Aims

Osteoarthritis (OA) is a common degenerative joint disease characterized by chronic inflammatory articular cartilage degradation. Long noncoding RNAs (lncRNAs) have been previously indicated to play an important role in inflammation-related diseases. Herein, the current study set out to explore the involvement of lncRNA H19 in OA.

Methods

Firstly, OA mouse models and interleukin (IL)-1β-induced mouse chondrocytes were established. Expression patterns of IL-38 were determined in the synovial fluid and cartilage tissues from OA patients. Furthermore, the targeting relationship between lncRNA H19, tumour protein p53 (TP53), and IL-38 was determined by means of dual-luciferase reporter gene, chromatin immunoprecipitation, and RNA immunoprecipitation assays. Subsequent to gain- and loss-of-function assays, the levels of cartilage damage and proinflammatory factors were further detected using safranin O-fast green staining and enzyme-linked immunosorbent assay (ELISA) in vivo, respectively, while chondrocyte apoptosis was measured using Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) in vitro.


Bone & Joint Research
Vol. 13, Issue 8 | Pages 411 - 426
28 Aug 2024
Liu D Wang K Wang J Cao F Tao L

Aims

This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

Methods

We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.


Bone & Joint 360
Vol. 13, Issue 4 | Pages 40 - 42
2 Aug 2024

The August 2024 Research Roundup360 looks at: Effect of vitamin D deficiency on periprosthetic joint infection and complications after primary total joint replacement; Postoperative angiotensin receptor blocker use associated with decreased rates of manipulation under anaesthesia in patients undergoing total knee arthroplasty; Central sensitization: the missing link between psychological distress and poor outcome following primary total knee arthroplasty; Thromboprophylaxis for the trauma and orthopaedic surgeon; Life expectancy after treatment of metastatic bone disease: an international trend analysis.


Bone & Joint Research
Vol. 13, Issue 2 | Pages 52 - 65
1 Feb 2024
Yao C Sun J Luo W Chen H Chen T Chen C Zhang B Zhang Y

Aims

To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism.

Methods

In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed.


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 6 - 8
1 Jan 2024
Stevenson J Cool P Ashford R

Cite this article: Bone Joint J 2024;106-B(1):6–8.


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

The February 2023 Oncology Roundup360 looks at: Is the number of national database research studies in musculoskeletal sarcoma increasing, and are these studies reliable?; Re-excision after unplanned excision of soft-tissue sarcoma is associated with high morbidity; Adjuvant radiation in atypical lipomatous tumours; The oncological outcomes of isolated limb perfusion and neoadjuvant radiotherapy in soft-tissue sarcoma patients - a nationwide multicentre study; Can low-grade chondrosarcoma be treated with intralesional curettage and cryotherapy?; Efficacy and safety of carbon ion radiotherapy for bone sarcomas: a systematic review and meta-analysis; Doxorubicin-polymeric meshes prevent local recurrence after sarcoma resection while avoiding cardiotoxicity; How important are skip lesions in Ewing’s sarcoma?; Improving outcomes for amputees: the health-related quality of life and cost utility analysis of osseointegration prosthetics in transfemoral amputees.


Bone & Joint Research
Vol. 6, Issue 5 | Pages 323 - 330
1 May 2017
Pijls BG Sanders IMJG Kuijper EJ Nelissen RGHH

Objectives. Infection of implants is a major problem in elective and trauma surgery. Heating is an effective way to reduce the bacterial load in food preparation, and studies on hyperthermia treatment for cancer have shown that it is possible to heat metal objects with pulsed electromagnetic fields selectively (PEMF), also known as induction heating. We therefore set out to answer the following research question: is non-contact induction heating of metallic implants effective in reducing bacterial load in vitro?. Methods. Titanium alloy cylinders (Ti6Al4V) were exposed to PEMF from an induction heater with maximum 2000 watts at 27 kHz after being contaminated with five different types of micro-organisms: Staphylococcus epidermidis; Staphylococcus aureus; Pseudomonas aeruginosa; spore-forming Bacillus cereus; and yeast Candida albicans. The cylinders were exposed to incremental target temperatures (35°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C) for up to 3.5 minutes. Results. There was an average linear heating rate of 0.39°C per second up to the target temperature, and thereafter the target temperature was maintained until the end of the experiment. At 60°C and higher (duration 3.5 minutes), there was a 6-log reduction or higher for every micro-organism tested. At 60°C, we found that the shortest duration of effective induction heating was 1.5 minutes. This resulted in a 5-log reduction or higher for every micro-organism tested. Conclusion. Non-contact induction heating of a titanium disk is effective in reducing bacterial load in vitro. These promising results can be further explored as a new treatment modality for infections of metal orthopaedic implants. Cite this article: B. G. Pijls, I. M. J. G. Sanders, E. J. Kuijper, R. G. H. H. Nelissen. Non-contact electromagnetic induction heating for eradicating bacteria and yeasts on biomaterials and possible relevance to orthopaedic implant infections: In vitro findings. Bone Joint Res 2017;6:323–330. DOI: 10.1302/2046-3758.65.BJR-2016-0308.R1


Bone & Joint 360
Vol. 12, Issue 5 | Pages 39 - 42
1 Oct 2023

The October 2023 Oncology Roundup360 looks at: Are pathological fractures in patients with osteosarcoma associated with worse survival outcomes?; Spotting the difference: how secondary osteosarcoma manifests in retinoblastoma survivors versus conventional cases; Accuracy of MRI scans in predicting intra-articular joint involvement in high-grade sarcomas around the knee; Endoprosthetic reconstruction for lower extremity soft-tissue sarcomas with bone involvement; Local relapse of soft-tissue sarcoma of the extremities or trunk wall operated on with wide margins without radiation therapy; 3D-printed, custom-made prostheses in patients who had resection of tumours of the hand and foot; Long-term follow-up for low-grade chondrosarcoma; Evaluation of local recurrence and diagnostic discordance in chondrosarcoma patients undergoing preoperative biopsy; Radiological scoring and resection grade for intraosseous chondrosarcoma.


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.


The Bone & Joint Journal
Vol. 98-B, Issue 12 | Pages 1682 - 1688
1 Dec 2016
Ghazala CG Agni NR Ragbir M Dildey P Lee D Rankin KS Beckingsale TB Gerrand CH

Aims. Myxofibrosarcomas (MFSs) are malignant soft-tissue sarcomas characteristically presenting as painless slowly growing masses in the extremities. Locally infiltrative growth means that the risk of local recurrence is high. We reviewed our experience to make recommendations about resection strategies and the role of the multidisciplinary team in the management of these tumours. Patients and Methods. Patients with a primary or recurrent MFS who were treated surgically in our unit between 1997 and 2012 were included in the study. Clinical records and imaging were reviewed. A total of 50 patients with a median age of 68.4 years (interquartile range 61.6 to 81.8) were included. There were 35 men; 49 underwent surgery in our unit. Results. The lower limb was the most common site (32/50, 64%). The mean size of the tumours was 8.95 cm (1.5 to 27.0); 26 (52%) were French Fédération Nationale des Centres de Lutte Contre le Cancer grade III. A total of 21 (43%) had positive margins after the initial excision; 11 underwent further excision. Histology showed microscopic spread of up to 29 mm beyond macroscopic tumour. Local recurrence occurred in seven patients (14%) at a mean of 21 months (3 to 33) and 15 (30%) developed metastases at a mean of 17 months (3 to 30) post-operatively. Conclusion. High rates of positive margins and the need for further excision makes this tumour particularly suited to management by multidisciplinary surgical teams. Microscopic tumour can be present up to 29 mm from the macroscopic tumour in fascially-based tumours. Cite this article: Bone Joint J 2016;98-B:1682–8


Bone & Joint Open
Vol. 4, Issue 8 | Pages 559 - 566
1 Aug 2023
Hillier DI Petrie MJ Harrison TP Salih S Gordon A Buckley SC Kerry RM Hamer A

Aims

The burden of revision total hip arthroplasty (rTHA) continues to grow. The surgery is complex and associated with significant costs. Regional rTHA networks have been proposed to improve outcomes and to reduce re-revisions, and therefore costs. The aim of this study was to accurately quantify the cost and reimbursement for a rTHA service, and to assess the financial impact of case complexity at a tertiary referral centre within the NHS.

Methods

A retrospective analysis of all revision hip procedures was performed at this centre over two consecutive financial years (2018 to 2020). Cases were classified according to the Revision Hip Complexity Classification (RHCC) and whether they were infected or non-infected. Patients with an American Society of Anesthesiologists (ASA) grade ≥ III or BMI ≥ 40 kg/m2 are considered “high risk” by the RHCC. Costs were calculated using the Patient Level Information and Costing System (PLICS), and remuneration based on Healthcare Resource Groups (HRG) data. The primary outcome was the financial difference between tariff and cost per patient episode.