Aims. The aim of this study was to report the patterns of symptoms and insufficiency fractures in patients with tumour-induced osteomalacia (TIO) to allow the early diagnosis of this rare condition. Methods. The study included 33 patients with TIO who were treated between January 2000 and June 2022. The causative tumour was detected in all patients. We investigated the symptoms and evaluated the radiological patterns of insufficiency fractures of the rib, spine, and limbs. Results. The mean age of the patients was 57 years (24 to 87), and the mean duration of pain from onset to time of presentation was 3.9 years (0.75 to 23). The primary symptoms were low back pain (ten patients), chest wall pain (eight patients), and hip pain (eight patients). There were symptoms at more sites at the time of presentation compared with that at the time of the onset of symptoms. Bone scans showed the uptake of tracer in the rib (100%), thoracic and lumbar vertebrae (83%), proximal femur (62%), distal femur (66%), and proximal tibia (72%). Plain radiographs or MRI scans identified femoral neck fractures in 14 patients, subchondral insufficiency fractures of the femoral head and knee in ten and six patients, respectively, distal femoral fractures in nine patients, and proximal tibial fractures in 12 patients. Thoracic or lumbar vertebral fractures were identified in 23 of 29 patients (79.3%) when using any imaging study, and a biconcave deformity was the most common type of fracture. Conclusion. Insufficiency fractures in patients with TIO caused spinal pain, chest wall pain, and periarticular pain in the lower limbs. Vertebral fractures tended to be biconcave deformities, and periarticular fractures of the hips and knees included subchondral insufficiency fractures and epiphyseal or metaphyseal fractures. In patients with a tumour, the presence of one or more of these symptoms and an insufficiency fracture should suggest the diagnosis of TIO. Cite this article: Bone Joint J 2023;105-B(5):568–574

Aims. The aim of this study was to assess the current trends in the estimation of survival and the preferred forms of treatment of pathological fractures among national and international general and oncological orthopaedic surgeons, and to explore whether improvements in the management of these patients could be identified in this way. Materials and Methods. All members of the Dutch Orthopaedic Society (DOS) and the European Musculoskeletal Oncology Society (EMSOS) were invited to complete a web-based questionnaire containing 12 cases. Results. A total of 96 of 948 members of the DOS (10.1%; groups 1 and 2) and 33 of 182 members of the EMSOS (18%; group 3) replied. The estimation of survival was accurate by more than 50% of all three groups, if the expected survival was short (< 3 months) or long (> 12 months). General orthopaedic surgeons preferred using an intramedullary nail for fractures of the humerus and femur, irrespective of the expected survival or the origin of primary tumour or the location of the fracture. Oncological orthopaedic surgeons recommended prosthetic reconstruction in patients with a long expected survival. Conclusion. Identifying patients who require centralized care, as opposed to those who can be adequately treated in a regional centre, can improve the management of patients with pathological fractures. This differentiation should be based on the expected survival, the type and extent of the tumour, and the location of the fracture. Cite this article: Bone Joint J 2018;100-B:1392–8

Aims. The aim of this paper was to investigate the prognostic factors for local recurrence in patients with pathological fracture through giant cell tumours of bone (GCTB). Patients and Methods. A total of 107 patients presenting with fractures through GCTB treated at our institution (Royal Orthopaedic Hospital, Birmingham, United Kingdom) between 1995 and 2016 were retrospectively studied. Of these patients, 57 were female (53%) and 50 were male (47%).The mean age at diagnosis was 33 years (14 to 86). A univariate analysis was performed, followed by multivariate analysis to identify risk factors based on the treatment and clinical characteristics. Results. The initial surgical treatment was curettage with or without adjuvants in 55 patients (51%), en bloc resection with or without reconstruction in 45 patients (42%), and neoadjuvant denosumab, followed by resection (n = 3, 3%) or curettage (n = 4, 4%). The choice of treatment depended on tumour location, Campanacci tumour staging, intra-articular involvement, and fracture displacement. Neoadjuvant denosumab was used only in fractures through Campanacci stage 3 tumours. Local recurrence occurred in 28 patients (25%). Surgery more than six weeks after the fracture did not affect the risk of recurrence in any of the groups. In Campanacci stage 3 tumours not treated with denosumab, en bloc resection had lower local recurrences (13%), compared with curettage (39%). In tumours classified as Campanacci 2, intralesional curettage and en bloc resections had similar recurrence rates (21% and 24%, respectively). After univariate analysis, the type of surgical intervention, location, and the use of denosumab were independent factors predicting local recurrence. Further surgery was required 33% more often after intralesional curettage in comparison with resections (mean 1.59, 0 to 5 vs 1.06, 0 to 3 operations). All patients treated with denosumab followed by intralesional curettage developed local recurrence. Conclusion. In patients with pathological fractures through GCTB not treated with denosumab, en bloc resection offers lower risks of local recurrence in tumours classified as Campanacci stage 3. Curettage or resections are both similar options in terms of the risk of local recurrence for tumours classified as Campanacci stage 2. The benefits of denosumab followed by intralesional curettage in these patients still remains unclear

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

Opinion remains divided as to whether the development of pathological fracture affects the prognosis of patients with an osteosarcoma of the extremities. We conducted a comprehensive systematic review and meta-analysis of papers which reported the outcomes of osteosarcoma patients with and without a pathological fracture. There were eight eligible papers for final analysis which reported on 1713 patients, of whom 303 (17.7%) had a pathological fracture. The mean age for 1464 patients in six studies was 23.2 years old (2 to 82). The mean follow-up for 1481 patients in seven studies was 90.1 months (6 to 240). The pooled estimates of local recurrence rates in osteosarcoma patients with and without pathological fractures were 14.4% (8.7 to 20.0) versus 11.4% (8.0 to 14.8). The pooled estimate of relative risk was 1.39 (0.89 to 2.20). The pooled estimates of five-year event-free survival rates in osteosarcoma patients with and without a pathological fracture were 49.3% (95% CI 43.6 to 54.9) versus 66.8% (95% CI 60.7 to 72.8). The pooled estimate of relative risk was 1.33 (1.12 to 1.59). There was no significant difference in the rate of local recurrence between patients who were treated by amputation or limb salvage. The development of a pathological fracture is a negative prognostic indicator in osteosarcoma and is associated with a reduced five-year event-free survival and a possibly higher rate of local recurrence. Our findings suggest that there is no absolute indication for amputation, as similar rates of local recurrence can be achieved in patients who are carefully selected for limb salvage. . Cite this article: Bone Joint J 2014; 96-B:1396–1403

We investigated whether the presence of a pathological fracture increased the risk of local recurrence in patients with a giant cell tumour (GCT) of bone. We also assessed if curettage is still an appropriate form of treatment in the presence of a pathological fracture. We conducted a comprehensive review and meta-analysis of papers which reported outcomes in patients with a GCT with and without a pathological fracture at presentation. We computed the odds ratio (OR) of local recurrence in those with and without a pathological fracture. . We selected 19 eligible papers for final analysis. This included 3215 patients, of whom 580 (18.0%) had a pathological fracture. The pooled OR for local recurrence between patients with and without a pathological fracture was 1.05 (95% confidence interval (CI) 0.66 to 1.67, p = 0.854). Amongst the subgroup of patients who were treated with curettage, the pooled OR for local recurrence was 1.23 (95% CI 0.75 to 2.01, p = 0.417). . A post hoc sample size calculation showed adequate power for both comparisons. . There is no difference in local recurrence rates between patients who have a GCT of bone with and without a pathological fracture at the time of presentation. The presence of a pathological fracture should not preclude the decision to perform curettage as carefully selected patients who undergo curettage can have similar outcomes in terms of local recurrence to those without such a fracture. Cite this article: Bone Joint J 2015;97-B:1566–71

Pathological fractures of the humerus are associated with pain, morbidity, loss of function and a diminished quality of life. We report our experience of stabilising these fractures using polymethylmethacrylate and non-locking plates. We undertook a retrospective review over 20 years of patients treated at a tertiary musculoskeletal oncology centre. Those who had undergone surgery for an impending or completed pathological humeral fracture with a diagnosis of metastatic disease or myeloma were identified from our database. There were 63 patients (43 men, 20 women) in the series with a mean age of 63 years (39 to 87). All had undergone intralesional curettage of the tumour followed by fixation with intramedullary polymethylmethacrylate and plating. Complications occurred in 14 patients (22.2%) and seven (11.1%) required re-operation. At the latest follow-up, 47 patients (74.6%) were deceased and 16 (25.4%) were living with a mean follow-up of 75 months (1 to 184). A total of 54 (86%) patients had no or mild pain and 50 (80%) required no or minimal assistance with activities of daily living. Of the 16 living patients none had pain and all could perform activities of daily living without assistance. Intralesional resection of the tumour, filling of the cavity with cement, and plate stabilisation of the pathological fracture gives immediate rigidity and allows an early return of function without the need for bony union. The patient’s local disease burden is reduced, which may alleviate tumour-related pain and slow the progression of the disease. The cemented-plate technique provides a reliable option for the treatment of pathological fractures of the humerus

Previously, we showed that case-specific non-linear finite element (FE) models are better at predicting the load to failure of metastatic femora than experienced clinicians. In this study we improved our FE modelling and increased the number of femora and characteristics of the lesions. We retested the robustness of the FE predictions and assessed why clinicians have difficulty in estimating the load to failure of metastatic femora. A total of 20 femora with and without artificial metastases were mechanically loaded until failure. These experiments were simulated using case-specific FE models. Six clinicians ranked the femora on load to failure and reported their ranking strategies. The experimental load to failure for intact and metastatic femora was well predicted by the FE models (R. 2. = 0.90 and R. 2. = 0.93, respectively). Ranking metastatic femora on load to failure was well performed by the FE models (τ = 0.87), but not by the clinicians (0.11 < τ < 0.42). Both the FE models and the clinicians allowed for the characteristics of the lesions, but only the FE models incorporated the initial bone strength, which is essential for accurately predicting the risk of fracture. Accurate prediction of the risk of fracture should be made possible for clinicians by further developing FE models.

A number of risk factors based upon mostly retrospective surgical data, have been formulated in order to identify impending pathological fractures of the femur from low-risk metastases. We have followed up patients taking part in a randomised trial of radiotherapy, prospectively, in order to determine if these factors were effective in predicting fractures. In 102 patients with 110 femoral lesions, 14 fractures occurred during follow-up. The risk factors studied were increasing pain, the size of the lesion, radiographic appearance, localisation, transverse/axial/circumferential involvement of the cortex and the scoring system of Mirels. Only axial cortical involvement > 30 mm (p = 0.01), and circumferential cortical involvement > 50% (p = 0.03) were predictive of fracture. Mirels’ scoring system was insufficiently specific to predict a fracture (p = 0.36). Our results indicate that most conventional risk factors overestimate the actual occurrence of pathological fractures of the femur. The risk factor of axial cortical involvement provides a simple, objective tool in order to decide which treatment is appropriate

Bone loss secondary to primary or metastatic lesions of the proximal humerus remains a challenging surgical problem. Options include preservation of the joint with stabilisation using internal fixation or resection of the tumour with prosthetic replacement. Resection of the proximal humerus often includes the greater tuberosity and adjacent diaphysis, which may result in poor function secondary to loss of the rotator cuff and/or deltoid function. Preservation of the joint with internal fixation may reduce the time in hospital and peri-operative morbidity compared with joint replacement, and result in a better functional outcome. We included 32 patients with pathological fractures of the proximal humerus in this study. Functional and radiological assessments were performed. At a mean follow-up of 17.6 months (8 to 61) there was no radiological evidence of failure of fixation. The mean revised musculoskeletal Tumour Society functional score was 94.6% (86% to 99%). There was recurrent tumour requiring further surgery in four patients (12.5%). Of the 22 patients who were employed prior to presentation all returned to work without restrictions. The use of a locking plate combined with augmentation with cement extends the indications for salvage of the proximal humerus with good function in patients with pathological and impending pathological fractures

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. Results. The median OS was 3.9 months (95% confidence interval (CI) 2.1 to 5.7). Patients with EGFR (15%) or kRAS mutations (34%) had a median OS of 17.3 months (95% CI 12.7 to 22.0) and 1.8 months (95% CI 1.0 to 2.7), respectively. Compared with EGFR-positive patients, EGFR-negative patients had a 2.5 times higher risk of death (95% CI 1.5 to 4.2). Incorporating EGFR mutation status in the prognostic model improved its discriminatory power. Conclusion. Survival prediction models for patients with symptomatic bone metastases are used to determine the most appropriate (surgical) treatment for painful or fractured lesions. This study shows that NSCLC should not be regarded as a single entity in such models. Cite this article: Bone Joint J 2017;99-B:516–21

Aims. Intra-articular (IA) tumours around the knee are treated with extra-articular (EA) resection, which is associated with poor functional outcomes. We aim to evaluate the accuracy of MRI in predicting IA involvement around the knee. Methods. We identified 63 cases of high-grade sarcomas in or around the distal femur that underwent an EA resection from a prospectively maintained database (January 1996 to April 2020). Suspicion of IA disease was noted in 52 cases, six had IA pathological fracture, two had an effusion, two had prior surgical intervention (curettage/IA intervention), and one had an osseous metastasis in the proximal tibia. To ascertain validity, two musculoskeletal radiologists (R1, R2) reviewed the preoperative imaging (MRI) of 63 consecutive cases on two occasions six weeks apart. The radiological criteria for IA disease comprised evidence of tumour extension within the suprapatellar pouch, intercondylar notch, extension along medial/lateral retinaculum, and presence of IA fracture. The radiological predictions were then confirmed with the final histopathology of the resected specimens. Results. The resection histology revealed 23 cases (36.5%) showing IA disease involvement compared with 40 cases without (62%). The intraobserver variability of R1 was 0.85 (p < 0.001) compared to R2 with κ = 0.21 (p = 0.007). The interobserver variability was κ = 0.264 (p = 0.003). Knee effusion was found to be the most sensitive indicator of IA involvement, with a sensitivity of 91.3% but specificity of only 35%. However, when combined with a pathological fracture, this rose to 97.5% and 100% when disease was visible in Hoffa’s fat pad. Conclusion. MRI imaging can sometimes overestimate IA joint involvement and needs to be correlated with clinical signs. In the light of our findings, we would recommend EA resections when imaging shows effusion combined with either disease in Hoffa’s fat pad or retinaculum, or pathological fractures. Cite this article: Bone Joint J 2023;105-B(6):696–701

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

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

Aims. Accurate estimations of the risk of fracture due to metastatic bone disease in the femur is essential in order to avoid both under-treatment and over-treatment of patients with an impending pathological fracture. The purpose of the current retrospective in vivo study was to use CT-based finite element analyses (CTFEA) to identify a clear quantitative differentiating factor between patients who are at imminent risk of fracturing their femur and those who are not, and to identify the exact location of maximal weakness where the fracture is most likely to occur. Methods. Data were collected on 82 patients with femoral metastatic bone disease, 41 of whom did not undergo prophylactic fixation. A total of 15 had a pathological fracture within six months following the CT scan, and 26 were fracture-free during the five months following the scan. The Mirels score and strain fold ratio (SFR) based on CTFEA was computed for all patients. A SFR value of 1.48 was used as the threshold for a pathological fracture. The sensitivity, specificity, positive, and negative predicted values for Mirels score and SFR predictions were computed for nine patients who fractured and 24 who did not, as well as a comparison of areas under the receiver operating characteristic curves (AUC of the ROC curves). Results. The sensitivity of SFR was 100% compared with 88% for the Mirels score, and the specificity of SFR was 67% compared with 38% for the Mirels score. The AUC was 0.905 for SFR compared with 0.578 for the Mirels score (p = 0.008). Conclusion. All the patients who sustained a pathological fracture of the femur had an SFR of > 1.48. CTFEA was far better at predicting the risk of fracture and its location accurately compared with the Mirels score. CTFEA is quick and automated and can be incorporated into the protocol of CT scanners. Cite this article: Bone Joint J 2020;102-B(5):638–645

Aims

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

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.

Aims. Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up. Methods. Patients with GCTB of the limb considered high-risk for unsuccessful joint salvage, due to minimal periarticular and subchondral bone, large soft tissue mass, or pathological fracture, were treated with Denosumab followed by extended intralesional curettage with the goal of preserving the joint surface. Patients were followed for local recurrence, metastasis, and secondary sarcoma. Results. A total of 25 patients with a mean age of 33.8 years (18 to 67) with high-risk GCTB received median six cycles of Denosumab before surgery. Tumours occurred most commonly around the knee (17/25, 68%). The median follow-up was 57 months (interquartile range (IQR) 13 to 88). The joint was salvaged in 23 patients (92%). Two required knee arthroplasty due to intra-articular fracture and arthritis. Local recurrence developed in 11 patients (44%) at a mean of 32.5 months (3 to 75) following surgery, of whom four underwent repeat curettage and joint salvage. One patient developed secondary osteosarcoma and another benign GCT lung metastases. Conclusion. The use of Denosumab for joint salvage was associated with a higher than expected rate of local recurrence at 44%. Neoadjuvant Denosumab for joint-sparing procedures should be considered with caution in light of these results. Cite this article: Bone Joint J 2021;103-B(1):184–191

Aims

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

Aims

Osteoarticular reconstruction of the distal femur in childhood has the advantage of preserving the tibial physis. However, due to the small size of the distal femur, matching the host bone with an osteoarticular allograft is challenging. In this study, we compared the outcomes and complications of a resurfaced allograft-prosthesis composite (rAPC) with those of an osteoarticular allograft to reconstruct the distal femur in children.