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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 51 - 51
22 Nov 2024
Nielsen MBD Jørgensen AR Stilling M Mikkelsen MKD Jørgensen N Bue M
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Aim

Efficacious antibiotic treatment is crucial for managing and preventing orthopedic infections due to their complexity and associated risk of treatment failure. Previous reviews on antibiotic target tissue concentrations have primarily focused on static measurements, which may not accurately reflect the dynamic pharmacokinetic/pharmacodynamic (PK/PD) changes encountered in clinical settings.

This review aimed to summarize the current literature on antibiotic distribution in orthopedically relevant tissues and settings using dynamic sampling methods.

Method

In accordance with PRISMA guidelines, a literature search was conducted with a scientific librarian's assistance. PubMed and Embase databases were systematically searched using relevant MeSH terms, entries, and keywords. English-published studies between 2004 and 2023 involving systemic antibiotic administration and dynamic measurements were included. 4467 titles were identified. After title and abstract screening, 77 eligible studies remained.


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. Results. Of the 3,814 patients with SREs, 3,159 (83%) patients had a single SRE and 655 (17%) patients developed a subsequent SRE. Patients who developed subsequent SREs generally had characteristics that favoured longer survival, such as higher BMI, higher albumin levels, fewer comorbidities, or lower neutrophil count. Once the patient got to the point of subsequent SRE, their clinical and oncological characteristics and one-year survival (28%) were not as good as those with only a single SRE (35%; p < 0.001), indicating that clinicians’ experiences when treating the initial SRE are not similar when treating a subsequent SRE. Conclusion. This study found that 17% of patients required treatments for a second, subsequent SRE, and the current clinical guideline did not provide a specific approach to this clinical condition. We observed that referencing the initial treatment, patients in the subsequent SRE group had longer six-week, 90-day, and one-year median survival than patients in the single SRE group. Once patients develop a subsequent SRE, they have a worse one-year survival rate than those who receive treatment for a single SRE. Future research should identify prognostic factors and assess the applicability of existing survival prediction models for better management of subsequent SREs. Cite this article: Bone Joint Res 2024;13(9):497–506


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. Results. A total of 846 patients with pelvic and appendicular MBD were analyzed, after excluding those with only spinal metastatic disease. A designated MBD lead was not present in 39% of centres (33/84). Adequate radiographs were not performed in 19% of patients (160/846), and 29% (247/846) did not have an up-to-date CT of thorax, abdomen, and pelvis to stage their disease. Compliance was low obtaining an oncological opinion (69%; 584/846) and prognosis estimations (38%; 223/846). Surgery was performed in 38% of patients (319/846), with the rates of up-to-date radiological investigations and oncology input with prognosis below the expected standard. Of the 25% (215/846) presenting with a solitary metastasis, a tertiary opinion from a MBD centre and biopsy was sought in 60% (130/215). Conclusion. Current practice in the UK does not comply with national guidelines, especially regarding investigations prior to surgery and for patients with solitary metastases. This study highlights the need for investment and improvement in care. The recent publication of British Orthopaedic Association Standards for Trauma (BOAST) defines auditable standards to drive these improvements for this vulnerable patient group. Cite this article: Bone Joint J 2023;105-B(10):1115–1122


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 101 - 101
1 Dec 2022
Abbott A Kendal J Moorman S Wajda B Schneider P Puloski S Monument M
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The presence of metastatic bone disease (MBD) often necessitates major orthopaedic surgery. Patients will enter surgical care either through emergent or electively scheduled care pathways. Patients in a pain crisis or with an acute fracture are generally admitted via emergent care pathways whereas patients with identified high-risk bone lesions are often booked for urgent yet scheduled elective procedures. The purpose of this study is to compare the post-operative outcomes of patients who present through emergent or electively scheduled care pathways in patients in a Canadian health care system. We have conducted a retrospective, multicenter cohort study of all patients presenting for surgery for MBD of the femur, humerus, tibia or pelvis in southern Alberta between 2006 and 2021. Patients were identified by a search query of all patients with a diagnosis of metastatic cancer who underwent surgery for an impending or actual pathologic fracture in the Calgary, South and Central Alberta Zones. Subsequent chart reviews were performed. Emergent surgeries were defined by patients admitted to hospital via urgent care mechanisms and managed via unscheduled surgical bookings (“on call list”). Elective surgeries were defined by patients seen by an orthopaedic surgeon at least once prior to surgery, and booked for a scheduled urgent, yet elective procedure. Outcomes include overall survival from the time of surgery, hospital length of stay, and 30-day hospital readmission rate. We have identified 402 patients to date for inclusion. 273 patients (67.9%) underwent surgery through emergent pathways and 129 patients (32.1%) were treated through urgent, electively scheduled pathways. Lung, prostate, renal cell, and breast cancer were the most common primary malignancies and there was no significant difference in these primaries amongst the groups (p=0.06). Not surprisingly, emergent patients were more likely to be treated for a pathologic fracture (p<0.001) whereas elective patients were more likely to be treated for an impending fracture (p<0.001). Overall survival was significantly shorter in the emergent group (5.0 months, 95%CI: 4.0-6.1) compared to the elective group (14.9 months 95%CI: 10.4-24.6) [p<0.001]. Hospital length of stay was significantly longer in the emergent group (13 days, 95%CI: 12-16 versus 5 days, 95%CI: 5-7 days). There was a significantly greater rate of 30-day hospital readmission in the emergent group (13.3% versus 7.8%) [p=0.01]. Electively managed MBD has multiple benefits including longer post-operative survival, shorter length of hospital stay, and a lower rate of 30-day hospital readmission. These findings from a Canadian healthcare system demonstrate clinical value in providing elective orthopaedic care when possible for patients with MBD. Furthermore, care delivery interventions capable of decreasing the footprint of emergent surgery through enhanced screening or follow-up of patients with MBD has the potential to significantly improve clinical outcomes in this population. This is an ongoing study that will justify refinements to the current surgical care pathways for MBD in order to identify patients prior to emergent presentation. Future directions will evaluate the costs associated with each care delivery method to provide opportunity for health economic efficiencies


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 100 - 100
1 Dec 2022
Wajda B Abbott A Kendal J Moorman S Schneider P Puloski S Monument M
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Metastatic bone disease (MBD) is a significant contributor to diminished quality of life in cancer patients, often leading to pathologic fractures, hypercalcaemia, intractable bone pain, and reduced functional independence. Standard of care management for MBD patients undergoing orthopaedic surgery is multi-disciplinary, includes regular surgical follow-up, case by case assessment for use of bone protective medications, and post-operative radiation therapy to the operative site. The number of patients in southern Alberta receiving standard of care post-operative management is currently unclear. Our aim is to develop a database of all patients in southern Alberta undergoing orthopaedic surgery for MBD and to assess for deficiencies and opportunities to ensure standard of care for this complex patient population. Patients were identified for database inclusion by a search query of the Alberta Cancer Registry of all patients with a diagnosis of metastatic cancer who underwent surgery for an impending or pathologic fracture in the Calgary, South and Central Alberta Zones. Demographic information, primary cancer history, previous local and systemic treatments, anatomical location of MBD event(s), surgical fixation techniques, and post-operative care details were collected. The rate of standard of care post-operative treatment was evaluated. A comparison of outcomes between tertiary urban centres and rural centres was also completed. Survival was calculated from time of first operation to date of death. Univariate and multivariate analyses were performed to identify the impact of post-operative care variables on survival amongst patients surviving longer than one month. We identified 402 patients who have undergone surgical treatment for MBD in southern Alberta from 2006-2018. Median age at time of surgery was 66.3 years and 52.7% of patients were female. Breast, lung, prostate, renal cell and multiple myeloma were the most common primary malignancies (n=328, 81.6%). Median post-operative survival was 6.8 months (95%CI: 5.7-8.3). 203 patients (52.5%) were treated with post-operative radiotherapy and 159 patients (50.8%) had post-operative surgical follow-up. Only 39 patients (11.3%) received bone protective agents in the peri-operative period. On multivariate survival analysis, post-operative surgical follow-up was associated with improved survival (p<0.001). Patients were treated at nine hospitals across southern Alberta with most patients treated in an urban center (65.9%). Post-operative survival was significantly longer amongst patients treated in an urban center (9.0 months, 95%CI: 6.9-12.3 versus 4.3 months, 95%CI: 3.4-5.6, p<0.001). The burden of MBD is significant and increasing. With treatment occurring at multiple provincial sites, there is a need for standardized, primary disease-specific peri- and post-operative protocols to ensure quality and efficacious patient care. To provide evidence informed treatment recommendations, we have developed a database of all patients in southern Alberta undergoing orthopaedic surgery for MBD. Our results demonstrate that many patients were not treated according to post-operative standard of care recommendations. Notably, half of the included patients did not have documented surgical follow-up, post-operative radiation treatment was low and only 11% were actively treated with bone protective agents. This data justifies the need for established surgical MBD care pathways and provides reference data to benchmark prospective QA and QI outcomes in this patient population


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 98 - 98
1 Dec 2022
Yamaura L Monument M Skeith L Schneider P
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Surgical management for acute or impending pathologic fractures in metastatic bone disease (MBD) places patients at high-risk for post-operative venous thromboembolism (VTE). Due to the combination of malignancy, systemic cancer treatment, and surgical treatment, VTE-risk is increased 7-fold in patients with MBD compared to non-cancer patients undergoing the same procedure. The extent and duration of post-operative hypercoagulability in patients with MBD remains unknown and thromboprophylaxis guidelines were developed for non-cancer patients, limiting their applicability to address the elevated VTE-risk in cancer patients. Thrombelastography (TEG) analysis is a point-of-care test that measures clot formation, stabilization, and lysis in whole blood samples. The TEG parameter, maximal amplitude (MA), indicates clot strength and the threshold of ≥65 mm has been used to define hypercoagulability and predict VTE events in non-cancer patients requiring orthopaedic surgery. Therefore, this study aims to quantify the extent and duration of post-operative hypercoagulability in patients with MBD using serial TEG analysis. Consecutive adults (≥18 years) with MBD who required orthopaedic surgery for acute or impending pathologic fractures were enrolled into this single-centre, prospective cohort study. Serial TEG analysis was performed onsite using a TEG®6s haemostasis analyzer (Haemonetics Corporation, Boston, MA) on whole blood samples collected at seven timepoints: pre-operatively; on post-operative day (POD) 1, 3, and 5; and at 2-, 6-, and 12-weeks post-operatively. Hypercoagulability was defined as MA ≥65 mm. Participants received standardized thromboprophylaxis for four weeks and patient-reported compliance with thromboprophylaxis was recorded. VTE was defined as symptomatic DVT or PE, or asymptomatic proximal DVT, and all participants underwent a screening post-operative lower extremity Doppler ultrasound on POD3. Descriptive statistics were performed and difference between pre-operative MA values of participants with VTE versus no VTE was evaluated using Student's t-test (p≤0.05). Twenty-one participants (10 female; 47.6%) with a mean age of 70 ± 12 years were enrolled. Nine different primary cancers were identified amongst participants, with breast (23.8%), colorectal (19.0%), and lung cancer (14.3%) most frequently reported. Most participants (57.1%) were hypercoagulable pre-operatively, and nearly half remained hypercoagulable at 6- and 12-weeks post-operatively (47.1 and 46.7%, respectively). VTE occurred in 5 patients (23.8%) and mean MA was 68.1 ± 4.6 mm at the time of diagnosis. Mean pre-operative MA values were significantly higher (p=0.02) in patients who experienced VTE (68.9 ± 3.5 mm) compared to those who did not (62.7 ± 6.5 mm). VTE incidence was highest in the first week post-operatively, during which time four VTE events (80%) occurred. The proportion of patients in a hypercoagulable state increased at three consecutive timepoints, beginning on POD3 (85.0%), increasing on POD5 (87.5%), and peaking at 2-weeks post-operatively (88.9%). Current thromboprophylaxis guidelines do not consider cancer-associated risk factors that contribute to increased VTE incidence and prescription duration may be inadequate to address prolonged post-operative hypercoagulability in patients with MBD. The high rate of VTE events observed and sustained hypercoagulable state indicate that thromboprophylaxis may be prematurely terminated while patients remain at high risk for VTE. Therefore, extending thromboprophylaxis duration beyond 4-weeks post-operatively in patients with MBD warrants further investigation


The Bone & Joint Journal
Vol. 103-B, Issue 10 | Pages 1633 - 1640
1 Oct 2021
Lex JR Evans S Parry MC Jeys L Stevenson JD

Aims

Proximal femoral endoprosthetic replacements (PFEPRs) are the most common reconstruction option for osseous defects following primary and metastatic tumour resection. This study aimed to compare the rate of implant failure between PFEPRs with monopolar and bipolar hemiarthroplasties and acetabular arthroplasties, and determine the optimum articulation for revision PFEPRs.

Methods

This is a retrospective review of 233 patients who underwent PFEPR. The mean age was 54.7 years (SD 18.2), and 99 (42.5%) were male. There were 90 patients with primary bone tumours (38.6%), 122 with metastatic bone disease (52.4%), and 21 with haematological malignancy (9.0%). A total of 128 patients had monopolar (54.9%), 74 had bipolar hemiarthroplasty heads (31.8%), and 31 underwent acetabular arthroplasty (13.3%).


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 63 - 63
1 Mar 2021
Bozzo A Deng J Bhasin R Deodat M Abbas U Wariach S Axelrod D Masrouha K Wilson D Ghert M
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Lung cancer is the most common cancer diagnosed, the leading cause of cancer-related deaths, and bone metastases occurs in 20–40% of lung cancer patients. They often present symptomatically with pain or skeletal related events (SREs), which are independently associated with decreased survival. Bone modifying agents (BMAs) such as Denosumab or bisphosphonates are routinely used, however no specific guidelines exist from the National Comprehensive Cancer Center or the European Society of Medical Oncologists. Perhaps preventing the formation of guidelines is the lack of a high-quality quantitative synthesis of randomized controlled trial (RCT) data to determine the optimal treatment for the patient important outcomes of 1) Overall survival (OS), 2) Time to SRE, 3) SRE incidence, and 4) Pain Resolution. The objective of this study was to perform the first systematic review and network meta-analysis (NMA) to assess the best BMA for treatment of metastatic lung cancer to bone. We conducted our study in accordance to the PRISMA protocol. We performed a librarian assisted search of MEDLINE, PubMed, EMBASE, and Cochrane Library and Chinese databases including CNKI and Wanfang Data. We included studies that are RCTs reporting outcomes specifically for lung cancer patients treated with a bisphosphonate or Denosumab. Screening, data extraction, risk of bias and GRADE were performed in duplicate. The NMA was performed using a Bayesian probability model with R. Results are reported as relative risks, odds ratios or mean differences, and the I2 value is reported for heterogeneity. We assessed all included articles for risk of bias and applied the novel GRADE framework for NMAs to rate the quality of evidence supporting each outcome. We included 132 RCTs comprising 11,161 patients with skeletal metastases from lung cancer. For OS, denosumab was ranked above zoledronic acid (ZA) and estimated to confer an average of 3.7 months (95%CI: −0.5 – 7.6) increased survival compared to untreated patients. For time to SRE, denosumab was ranked first with an average of 9.1 additional SRE-free months (95%CI: 4.0 – 14.0) compared to untreated patients, while ZA conferred an additional 4.8 SRE-free months (2.4 – 7.0). Patients treated with the combination of Ibandronate and systemic therapy were 2.3 times (95%CI: 1.7 – 3.2) more likely to obtain successful pain resolution, compared to untreated. Meta-regression showed no effect of heterogeneity length of follow-up or pain scales on the observed treatment effects. Heterogeneity in the network was considered moderate for overall survival and time to SRE, mild for SRE incidence, and low for pain resolution. While a generally high risk of bias was observed across studies, whether they were from Western or Chinese databases. The overall GRADE for the evidence underlying our results is High for Pain control and SRE incidence, and Moderate for OS and time to SRE. This study represents the most comprehensive synthesis of the best available evidence guiding pharmacological treatment of bone metastases from lung cancer. Denosumab is ranked above ZA for both overall survival and time to SRE, but both treatments are superior to no treatment. ZA was first among all bisphosphonates assessed for odds of reducing SRE incidence, while the combination of Ibandronate and radionuclide therapy was most effective at significantly reducing pain from metastases. Clinicians and policy makers may use this synthesis of all available RCT data as support for the use of a BMA in MBD for lung cancer


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


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_8 | Pages 79 - 79
1 Aug 2020
Bozzo A Ghert M Reilly J
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Advances in cancer therapy have prolonged patient survival even in the presence of disseminated disease and an increasing number of cancer patients are living with metastatic bone disease (MBD). The proximal femur is the most common long bone involved in MBD and pathologic fractures of the femur are associated with significant morbidity, mortality and loss of quality of life (QoL). Successful prophylactic surgery for an impending fracture of the proximal femur has been shown in multiple cohort studies to result in longer survival, preserved mobility, lower transfusion rates and shorter post-operative hospital stays. However, there is currently no optimal method to predict a pathologic fracture. The most well-known tool is Mirel's criteria, established in 1989 and is limited from guiding clinical practice due to poor specificity and sensitivity. The ideal clinical decision support tool will be of the highest sensitivity and specificity, non-invasive, generalizable to all patients, and not a burden on hospital resources or the patient's time. Our research uses novel machine learning techniques to develop a model to fill this considerable gap in the treatment pathway of MBD of the femur. The goal of our study is to train a convolutional neural network (CNN) to predict fracture risk when metastatic bone disease is present in the proximal femur. Our fracture risk prediction tool was developed by analysis of prospectively collected data of consecutive MBD patients presenting from 2009–2016. Patients with primary bone tumors, pathologic fractures at initial presentation, and hematologic malignancies were excluded. A total of 546 patients comprising 114 pathologic fractures were included. Every patient had at least one Anterior-Posterior X-ray and clinical data including patient demographics, Mirel's criteria, tumor biology, all previous radiation and chemotherapy received, multiple pain and function scores, medications and time to fracture or time to death. We have trained a convolutional neural network (CNN) with AP X-ray images of 546 patients with metastatic bone disease of the proximal femur. The digital X-ray data is converted into a matrix representing the color information at each pixel. Our CNN contains five convolutional layers, a fully connected layers of 512 units and a final output layer. As the information passes through successive levels of the network, higher level features are abstracted from the data. The model converges on two fully connected deep neural network layers that output the risk of fracture. This prediction is compared to the true outcome, and any errors are back-propagated through the network to accordingly adjust the weights between connections, until overall prediction accuracy is optimized. Methods to improve learning included using stochastic gradient descent with a learning rate of 0.01 and a momentum rate of 0.9. We used average classification accuracy and the average F1 score across five test sets to measure model performance. We compute F1 = 2 x (precision x recall)/(precision + recall). F1 is a measure of a model's accuracy in binary classification, in our case, whether a lesion would result in pathologic fracture or not. Our model achieved 88.2% accuracy in predicting fracture risk across five-fold cross validation testing. The F1 statistic is 0.87. This is the first reported application of convolutional neural networks, a machine learning algorithm, to this important Orthopaedic problem. Our neural network model was able to achieve reasonable accuracy in classifying fracture risk of metastatic proximal femur lesions from analysis of X-rays and clinical information. Our future work will aim to externally validate this algorithm on an international cohort


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Cervical spinal arthrodesis is the standard of care for the treatment of spinal diseases induced neck pain. However, adjacent segment disease (ASD) is the primary postoperative complication, which draws great concerns. At present, controversy still exists for the etiology of ASD. Knowledge of cervical spinal loading pattern after cervical spinal arthrodesis is proposed to be the key to answer these questions. Musculoskeletal (MSK) multi-body dynamics (MBD) models have an opportunity to obtain spinal loading that is very difficult to directly measure in vivo. In present study, a previously validated cervical spine MSK MBD model was developed for simulating cervical spine after single-level anterior arthrodesis at C5-C6 disc level. In this cervical spine model, postoperative sagittal alignment and spine rhythms of each disc level, different from normal healthy subject, were both taken into account. Moreover, the biomechanical properties of facet joints of adjacent levels after anterior arthrodesis were modified according to the experimental results. Dynamic full range of motion (ROM) flexion/extension simulation was performed, where the motion data after arthrodesis was derived from published in-vivo kinematic observations. Meanwhile, the full ROM flexion/extension of normal subject was also simulated by the generic cervical spine model for comparative purpose. The intervertebral compressive and shear forces and loading-sharing distribution (the proportions of intervertebral compressive and shear force and facet joint force) at adjacent levels (C3-C4, C4-C5 and C6-C7 disc levels) were then predicted. By comparison, arthrodesis led to a significant increase of adjacent intervertebral compressive force during the head extension movement. Postoperative intervertebral compressive forces at adjacent levels increased by approximate 20% at the later stage of the head extension movement. However, there was no obvious alteration in adjacent intervertebral compressive force, during the head flexion movement. For the intervertebral shear forces in the anterior-posterior direction, no significant differences were found between the arthrodesis subject and normal subject, during the head flexion/extension movement. Meanwhile, cervical spinal loading-sharing distribution after anterior arthrodesis was altered compared with the normal subject's distribution, during the head extension movement. In the postoperative loading-sharing distribution, the percentage of intervertebral disc forces was further increased as the motion angle increased, compared with normal subject. In conclusion, cervical spinal loading after anterior arthrodesis was significantly increased at adjacent levels, during the head extension movement. Cervical spine musculoskeletal MBD model provides an attempt to comprehend postoperative ASD after anterior arthrodesis from a biomechanical perspective


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_7 | Pages 96 - 96
1 Jul 2020
Bozzo A Ghert M
Full Access

Advances in cancer therapy have prolonged cancer patient survival even in the presence of disseminated disease and an increasing number of cancer patients are living with metastatic bone disease (MBD). The proximal femur is the most common long bone involved in MBD and pathologic fractures of the femur are associated with significant morbidity, mortality and loss of quality of life (QoL). Successful prophylactic surgery for an impending fracture of the proximal femur has been shown in multiple cohort studies to result in patients more likely to walk after surgery, longer survival, lower transfusion rates and shorter post-operative hospital stays. However, there is currently no optimal method to predict a pathologic fracture. The most well-known tool is Mirel's criteria, established in 1989 and is limited from guiding clinical practice due to poor specificity and sensitivity. The goal of our study is to train a convolutional neural network (CNN) to predict fracture risk when metastatic bone disease is present in the proximal femur. Our fracture risk prediction tool was developed by analysis of prospectively collected data for MBD patients (2009–2016) in order to determine which features are most commonly associated with fracture. Patients with primary bone tumors, pathologic fractures at initial presentation, and hematologic malignancies were excluded. A total of 1146 patients comprising 224 pathologic fractures were included. Every patient had at least one Anterior-Posterior X-ray. The clinical data includes patient demographics, tumor biology, all previous radiation and chemotherapy received, multiple pain and function scores, medications and time to fracture or time to death. Each of Mirel's criteria has been further subdivided and recorded for each lesion. We have trained a convolutional neural network (CNN) with X-ray images of 1146 patients with metastatic bone disease of the proximal femur. The digital X-ray data is converted into a matrix representing the color information at each pixel. Our CNN contains five convolutional layers, a fully connected layers of 512 units and a final output layer. As the information passes through successive levels of the network, higher level features are abstracted from the data. This model converges on two fully connected deep neural network layers that output the fracture risk. This prediction is compared to the true outcome, and any errors are back-propagated through the network to accordingly adjust the weights between connections. Methods to improve learning included using stochastic gradient descent with a learning rate of 0.01 and a momentum rate of 0.9. We used average classification accuracy and the average F1 score across test sets to measure model performance. We compute F1 = 2 x (precision x recall)/(precision + recall). F1 is a measure of a test's accuracy in binary classification, in our case, whether a lesion would result in pathologic fracture or not. Five-fold cross validation testing of our fully trained model revealed accurate classification for 88.2% of patients with metastatic bone disease of the proximal femur. The F1 statistic is 0.87. This represents a 24% error reduction from using Mirel's criteria alone to classify the risk of fracture in this cohort. This is the first reported application of convolutional neural networks, a machine learning algorithm, to an important Orthopaedic problem. Our neural network model was able to achieve impressive accuracy in classifying fracture risk of metastatic proximal femur lesions from analysis of X-rays and clinical information. Our future work will aim to validate this algorithm on an external cohort


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_7 | Pages 82 - 82
1 Jul 2020
Barton K Hazenbiller O Monument M Puloski S Freeman G Ball M Aboutaha A
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The burden of metastatic bone disease (MBD) in our Canadian cancer population continues to increase. MBD has a significant effect on patient morbidity, mortality, and health-related quality of life (HRQOL). There are various technical options used to surgically stabilize MBD lesions, surgical decision-making is variable and largely dependent on anatomic and surgeon-based factors. There is a paucity of research examining how surgical decision-making for MBD can be modified or individualized to improve quality of life (QOL) and functional outcomes, while more accurately aligning with patient-reported goals and expectations. The objective of this study was tosurvey MBD patients, support persons, physicians, and allied health care providers (HCP) with the goal of identifying 1) important contributors to HRQOL, 2) discordance in peri-operative expectations, and 3) perceived measures of success in the surgical management of MBD. This project is a longitudinal patient-engaged research initiative in MBD. A survey was developed based on HRQOL themes in the literature and based on feedback from our patient research partners. Participants were asked to identify 1) important contributors to HRQOL and 2) perceived measures of success relevant to the surgical management of MBD. Participants were asked to rank themes from ‘extremely important’ to ‘not important at all’. Using open-ended questions, participants were asked to identify areas of improvement. Responses from the open-ended questions were analyzed by an experienced qualitative researcher using conventional content analysis. Participant's demographics were calculated using descriptive statistics. Concordance or discordance of perceived measure of success was assessed via a Chi-Square test of independence. All statistical analyses were performed using IBM SPSS® software. Nine patients, seven support persons, 23 orthopaedic surgeons, 11 medical oncologists, 16 radiation oncologists, 16 nurses, and eight physiotherapists completed the survey. Regarding perceived measures of success, increased life expectancy (p Two main themes emerged around the timeliness of surgical care and the coordination of multidisciplinary care from patients and support persons. Patients and support persons expressed a sense of urgency in progressing to surgery/treatment, and frustration at perceived delays in treatment. Within coordination of care, patients and support persons would like clearer communication from the health care team. There is discordance between patient/support person goals compared to physicians/HCP goals in the surgical management of MBD. Surgical decision-making and operative techniques that minimize disease progression and improve survival are important to MBD patients. Timely access to surgery/surgical consultation and improved multidisciplinary communication is important to patients. This data suggests improved peri-operative communication and education is needed for MBD patients. Furthermore, future research evaluating how modern orthopaedic surgical techniques influence survival and disease progression in MBD is highly relevant and important to patients with MBD


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_1 | Pages 6 - 6
1 Jan 2019
Downie S Clift B Jariwala A Gupta S Mahendra A
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National guidelines recommend that trauma centres have a designated consultant for managing metastatic bone disease (MBD). No such system exists in Scotland. We compared MBD cases in a trauma hospital to a national bone tumour centre to characterise differences in management and outcome. Consecutive patients with metastatic proximal femoral lesions referred to a trauma unit and a national sarcoma centre were compared over a seven-year period (minimum follow-up one year). From Jan 2010-Dec 2016, 195 patients were referred to the trauma unit and 68 to the tumour centre. The trauma unit tended to see older patients (mean 72 vs. 65 years, p<0001) with cancers of poorer prognosis (e.g. 31% 61/195 vs. 13% 9/68 lung primary, p<0.001). Both units had similar operative rates but patients referred to the tumour centre were more likely to have endoprosthetic reconstruction (EPR 44% tumour vs. 3% trauma centre, p<0.001). Patients with an EPR survived longer than those with other types of fixation (81% 17/21 vs. 31% 35/112 one-year survival, p<0.001). Patients undergoing EPR were more likely to have an isolated metastasis (62% 13/21 vs. 17% 4/24, p<0.001). One patient from each centre had a revision for failed metalwork. There was a difference in caseload referred to both units, with the tumour centre seeing younger patients with a better prognosis. Patients suitable for endoprostheses were more likely to have isolated metastatic disease and a longer survival after surgery. An MBD pathway is required to ensure such patients are identified and referred for specialist management where appropriate


Bone & Joint Research
Vol. 6, Issue 1 | Pages 31 - 42
1 Jan 2017
Kang K Koh Y Jung M Nam J Son J Lee Y Kim S Kim S

Objectives

The aim of the current study was to analyse the effects of posterior cruciate ligament (PCL) deficiency on forces of the posterolateral corner structure and on tibiofemoral (TF) and patellofemoral (PF) contact force under dynamic-loading conditions.

Methods

A subject-specific knee model was validated using a passive flexion experiment, electromyography data, muscle activation, and previous experimental studies. The simulation was performed on the musculoskeletal models with and without PCL deficiency using a novel force-dependent kinematics method under gait- and squat-loading conditions, followed by probabilistic analysis for material uncertain to be considered.


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 Research
Vol. 2, Issue 6 | Pages 96 - 101
1 Jun 2013
Harvie P Whitwell D

Objectives. Guidelines for the management of patients with metastatic bone disease (MBD) have been available to the orthopaedic community for more than a decade, with little improvement in service provision to this increasingly large patient group. Improvements in adjuvant and neo-adjuvant treatments have increased both the number and overall survival of patients living with MBD. As a consequence the incidence of complications of MBD presenting to surgeons has increased and is set to increase further. The British Orthopaedic Oncology Society (BOOS) are to publish more revised detailed guidelines on what represents ‘best practice’ in managing patients with MBD. This article is designed to coincide with and publicise new BOOS guidelines and once again champion the cause of patients with MBD. . Methods. A series of short cases highlight common errors frequently being made in managing patients with MBD despite the availability of guidelines. Results. Despite guidelines for the management of patients with MBD being available for more than a decade basic errors in management continue to be made, affecting patient survival and quality of life. Conclusions. It is hoped that by publicising the new BOOS guidelines the management of patients with MBD will improve over the next decade, significantly more than it has over the last decade


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 103 - 103
1 Sep 2012
Arastu M Rashid A Haque S Bendall S
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Introduction. The rising incidence of metastatic bone disease (MBD) in the UK poses a significant management problem. Poorly defined levels of service provision have meant that improvements in patient prognosis have been mediocre at best. For that reason the British Orthopaedic Association (BOA) in conjunction with the British Orthopaedic Oncology Society (BOOS) issued guidelines in 2002 on good practice in the management of MBD. Despite the availability of these standards, there is very little robust data available for audit. The aim of this study was to conduct a regional survey of how these guidelines are being used in the management of MBD. Methods. A questionnaire was designed with 9 multiple choice questions representing the most common MBD scenarios. This was posted to 106 Consultant Orthopaedic Surgeons in 12 NHS Trusts in the South East of England. Results. The overall response rate to the questionnaire was 44%. There was considerable variation in the management of solitary femoral diaphyseal lesions, pathological subtrochanteric and intertrochanteric femoral neck fractures and vertebral metastases. Furthermore only 2 out of the 12 Trusts surveyed had a designated MBD lead as per the BOA/BOOS guidelines. Discussion. Our study reflects the variation in the management of MBD throughout the region, which may in turn be linked to poorer clinical outcomes. The results demonstrate the possibility of (i) inappropriate initial treatment, (ii) subsequent late tertiary referral and (iii) poor understanding of the biomechanical basis of orthopaedic implants, with the potential for inappropriate choice of prostheses and high failure rates. Streamlining cancer care will involve establishing regional MBD units within large centres where multidisciplinary services are available. Consequently all surrounding hospitals will need a designated MBD lead that can function as a conduit to this integrated care for selected patients


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVII | Pages 19 - 19
1 May 2012
Sloan S McAlinden M
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The management of pathological fractures due to Metastatic Bone Disease (MBD) and Primary Bone Tumours (PBTs) has implications for the Trauma service due to the extra pressures on staff, service delivery and budgets. We undertook an analysis of a cohort of patients presenting with MBD and PBTs. A retrospective chart review of all cases with MBD and PBTs admitted to a 40-bed Trauma Unit between 2005 and 2009 was conducted. The study looked at frequency, primary pathology, and site of pathology/fracture, time from primary diagnosis to referral, subsequent interventions and others. The results identified 34 patients, 21 females (62%) and 13 males (38%) (mean age: 64.6 years) with MBD or PBTs. Metastases secondary to breast cancer (n=13, 38%) and Myeloma (n=5, 15%) were the most common with the majority being found in the femur (n=22, 65%) and the Humerus (n=6, 18%). The mean time from primary tumour diagnosis to fracture referral was 29.6 months with 27 (79%) patients undergoing definitive surgical management within the unit. The conclusions of the study demonstrate that a wide variety of pathology presented to the unit over a 5 year period. Considerable variation was noted in the time from primary tumour diagnosis to presentation with a fracture. This could be due to improvements in treatments of specific cancers or a lack of understanding of what an Orthopaedic surgeon can offer the cancer patient. No definitive increase in pathological fractures was seen. The consensus opinion is that prompt and appropriate management of pathological fractures in cancer patients is cost effective. Management of these injuries, in a Trauma Unit, represents a small, but significant part of the annual work-load. While no significant trend has been seen, with respect to an increased incidence, it is noted that a proportion of these patients were a number of years from their initial diagnosis. With improvements in the survivorship of cancer patients, close scrutiny will be required to determine whether this ultimately translates into an increased fracture burden


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_I | Pages 78 - 78
1 Jan 2011
Arastu MH Rashid A Haque S Bendall S
Full Access

Introduction: The rising incidence of metastatic bone disease (MBD) in the UK poses a significant management problem. Poorly defined levels of service provision have meant that improvements in patient prognosis have been mediocre at best. For that reason the British Orthopaedic Association (BOA) in conjunction with the British Orthopaedic Oncology Society (BOOS) issued guidelines in 2002 on good practice in the management of MBD. Despite the availability of these standards, there is very little robust data available for audit. The aim of this study was to conduct a regional survey of how these guidelines are being used in the management of MBD. Methods: A questionnaire was designed with 9 multiple choice questions representing the most common MBD scenarios. This was posted to 106 Consultant Orthopaedic Surgeons in 12 NHS Trusts in the South East of England. Results: The overall response rate to the questionnaire was 44%. There was considerable variation in the management of solitary femoral diaphyseal lesions, pathological subtrochanteric and intertrochanteric femoral neck fractures and vertebral metastases. Furthermore only 2 out of the 12 Trusts surveyed had a designated MBD lead as per the BOA/BOOS guidelines. Discussion: Our study reflects the variation in the management of MBD throughout the region, which may in turn be linked to poorer clinical outcomes. The results demonstrate the possibility of. inappropriate initial treatment,. subsequent late tertiary referral and. poor understanding of the biomechanical basis of orthopaedic implants, with the potential for inappropriate choice of prostheses and high failure rates. Streamlining cancer care will involve establishing regional MBD units within large centres where multidisciplinary services are available. Consequently all surrounding hospitals will need a designated MBD lead that can function as a conduit to this integrated care for selected patients