Internal validation of modified Mirels' scoring system for pathologic femur fractures.

BACKGROUND: The proximal femur is a common site of bone metastasis. The Mirels' score is a frequently utilized system to identify patients at risk for pathologic fracture and while it has consistently demonstrated strong sensitivity, specificity has been relatively poor. Our group previously developed a Modified Mirels' scoring system which demonstrated improved ability to predict cases at risk of fracture in this patient population through modification of the Mirels' location score. The purpose of the present study is to internally validate this newly developed scoring system on an independent patient series. METHODS: Retrospective review was performed to identify patients who were evaluated for proximal femoral bone lesions. Patients were stratified into one of two groups: 1) those who went on to fracture within 4 months after initial evaluation (Fracture Group) and 2) those who did not fracture within 4 months of initial evaluation (No Fracture Group). Retrospective chart review was performed to assign an Original Mirels' (OM) Score and Modified Mirels' (MM) score to each patient at the time of initial evaluation. Descriptive statistics, logistic regression, receiver operating curve, and net benefit analyses were performed to determine the predictability of fractures when utilizing both scoring systems. RESULTS: The use of the MM scoring improved fracture prediction over OM scoring for patients observed over a 4 month follow up based on logistic regression. Decision curve analysis showed that there was a net benefit using the MM score over the OM scoring for a full range of fracture threshold probabilities. Fracture prevalence was similar for current internal validation dataset when compared to the dataset of our index study with a comparable reduction in misclassification of fracture prediction when utilizing the modified scoring system versus the original. CONCLUSIONS: Use of MM scoring was found to improve fracture prediction over OM scoring when tested on an internal validation set of patients with disseminated metastatic lesions to the proximal femur. The improvement in fracture prediction demonstrated in the present study mirrored the results of our index study during which the MM system was developed.

The Role of Surveillance in Predicting Fracture in Pediatric Patients With Incidentally Discovered Nonossifying Fibromas and Fibrous Cortical Defects: Is It Worth It?

BACKGROUND: Nonossifying fibroma (NOF) and fibrous cortical defect (FCDs), the most common benign pediatric bone lesions, are usually incidental x-ray findings. Surveillance of characteristic lesions has been recommended to monitor for enlargement and assess fracture risk. However, no accepted fracture risk prediction guidelines exist, so indications for prophylactic surgery are unclear. The study's purposes were to (1) characterize the timing of NOF/FCD-associated fractures, (2) quantify the resources devoted to surveillance, and (3) evaluate the potential for surveillance to prevent pathologic fracture. METHODS: A single institution retrospective review was conducted to identify pediatric patients (below 18 y old) with clinical-radiographic documentation of an NOF or FCD diagnosis from 2012 to 2020. Patients who presented with fracture were tallied but excluded from the surveillance analysis. Patients without at least one follow-up visit were also excluded. Lesional radiographic features were characterized on initial imaging. The number of visits and imaging studies devoted to surveillance were tabulated. The number of fractures and prophylactic surgeries were recorded to quantify the potential of surveillance to prevent pathologic fractures. RESULTS: The study population presenting without fracture consisted of 301 patients with 364 lesions with a mean follow-up of 20 months. By contrast, over the same period, 38 patients presented with NOF/FCD associated pathologic fractures. Surveillance included 1037 additional imaging tests over 1311 follow-up visits, or on average, 3.4 imaging studies and 4.4 visits per patient. During surveillance, only 2 (0.55%) lesions fractured. Another 10/364 (2.8%) patients underwent curettage and grafting, suggesting that-at best-the potential for preventing pathologic fracture by surveillance, assuming all 10 patients who underwent surgery would have subsequently fractured along with the 2 documented fractures, is 3.3% of lesions (12/364). CONCLUSIONS: The small number of fractures and surgeries during the follow-up period probably does not justify additional resources for surveillance beyond the initial visit, except in symptomatic patients with large lesions. However, subsequent visits may play a role in educating patients and their families regarding the natural history of these lesions. LEVEL OF EVIDENCE: Prognostic Level II-retrospective study.

Modification to Mirels scoring system location component improves fracture prediction for metastatic disease of the proximal femur.

BACKGROUND: Correctly identifying patients at risk of femoral fracture due to metastatic bone disease remains a clinical challenge. Mirels criteria remains the most widely referenced method with the advantage of being easily calculated but it suffers from poor specificity. The purpose of this study was to develop and evaluate a modified Mirels scoring system through scoring modification of the original Mirels location component within the proximal femur. METHODS: Computational (finite element) experiments were performed to quantify strength reduction in the proximal femur caused by simulated lytic lesions at defined locations. Virtual spherical defects representing lytic lesions were placed at 32 defined locations based on axial (4 axial positions: neck, intertrochanteric, subtrochanteric or diaphyseal) and circumferential (8 circumferential: 45-degree intervals) positions. Finite element meshes were created, material property assignment was based on CT mineral density, and femoral head/greater trochanter loading consistent with stair ascent was applied. The strength of each femur with a simulated lesion divided by the strength of the intact femur was used to calculate the Location-Based Strength Fraction (LBSF). A modified Mirels location score was next defined for each of the 32 lesion locations with an assignment of 1 (LBSF > 75%), 2 (LBSF: 51-75%), and 3 (LBSF: 0-50%). To test the new scoring system, data from 48 patients with metastatic disease to the femur, previously enrolled in a Musculoskeletal Tumor Society (MSTS) cross-sectional study was used. The lesion location was identified for each case based on axial and circumferential location from the CT images and assigned an original (2 or 3) and modified (1,2, or 3) Mirels location score. The total score for each was then calculated. Eight patients had a fracture of the femur and 40 did not over a 4-month follow-up period. Logistic regression and decision curve analysis were used to explore relationships between clinical outcome (Fracture/No Fracture) and the two Mirels scoring methods. RESULTS: The location-based strength fraction (LBSF) was lowest for lesions in the subtrochanteric and diaphyseal regions on the lateral side of the femur; lesions in these regions would be at greatest risk of fracture. Neck lesions located at the anterior and antero-medial positions were at the lowest risk of fracture. When grouped, neck lesions had the highest LBSF (83%), followed by intertrochanteric (72%), with subtrochanteric (50%) and diaphyseal lesions (49%) having the lowest LBSF. There was a significant difference (p < 0.0001) in LBSF between each axial location, except subtrochanteric and diaphyseal which were not different from each other (p = 0.96). The area under the receiver operator characteristic (ROC) curve using logistic regression was greatest for modified Mirels Score using site specific location of the lesion (Modified Mirels-ss, AUC = 0.950), followed by a modified Mirels Score using axial location of lesion (Modified Mirels-ax, AUC = 0.941). Both were an improvement over the original Mirels score (AUC = 0.853). Decision curve analysis was used to quantify the relative risks of identifying patients that would fracture (TP, true positives) and those erroneously predicted to fracture (FP, false positives) for the original and modified Mirels scoring systems. The net benefit of the scoring system weighed the benefits (TP) and harms (FP) on the same scale. At a threshold probability of fracture of 10%, use of the modified Mirels scoring reduced the number of false positives by 17-20% compared to Mirels scoring. CONCLUSIONS: A modified Mirels scoring system, informed by detailed analysis of the influence of lesion location, improved the ability to predict impending pathological fractures of the proximal femur for patients with metastatic bone disease. Decision curve analysis is a useful tool to weigh costs and benefits concerning fracture risk and could be combined with other patient/clinical factors that contribute to clinical decision making.

Evaluation of triage tool for low-grade cartilage tumors: Four-quadrant approach.

BACKGROUND AND OBJECTIVES: The "four-quadrant approach" (FQA) for triage of benign enchondromas (E) and low-grade malignant chondrosarcomas (LGC) divides patients into treatment categories based on the presence or absence of pain and observation of aggressive or benign radiographic features. This article evaluates the usefulness of the FQA in predicting E versus LGC and operative versus nonoperative outcome. METHODS: Patients had working diagnosis of E or LGC, 1-year minimum follow-up, imaging, clinical data, outcomes, and no radiographic evidence of high-grade chondrosarcoma. Statistical analysis determined whether quadrant distribution correlated to E versus LGC and operative versus nonoperative intervention. RESULTS: Of 56 lesions (49 patients), 9 were LGC and 47 E. Twenty-five lesions (all 9 LGC, 16 E) were treated operatively and 31 (all E) nonoperatively. There were statistically significant correlations between quadrant distribution and both tumor type (p = 1.9 × 10-6 ) and operative intervention (p = 6.28 × 10-6 ). CONCLUSIONS: The FQA is a promising diagnostic tool to distinguish between E and LGC hyaline cartilage tumors, along with determining operative versus nonoperative intervention. Prospective evaluation is warranted.

Atypical Enostoses-Series of Ten Cases and Literature Review.

Bone islands (BI; enostoses) may be solitary or occur in the setting of osteopoikilosis (multiple bone islands) and are sometimes associated with Gardner's Syndrome (osteopoikilosis and colonic polyposis). Characteristic features of bone islands are (1) absence of pain or local tenderness, (2) typical radio dense central appearance with peripheral radiating spicules (rose thorn), (3) Mean CT (computerized tomography) attenuation values above 885 Hounsfield units (HU) (4) absence of uptake on bone scan and (5) radiographic stability over time. However, when enostoses display atypical features of pain, unusual radiographic appearance, aberrant HU, increased radiotracer uptake, and/or enlargement, they can be difficult to differentiate from more sinister bony lesions such as osteoblastic metastasis, low grade central osteosarcoma, osteoid osteoma and osteoblastoma. In this retrospective case series, the demographic, clinical, radiographic, treatment and outcome for ten patients with eleven atypical bone islands (ABI) are presented, some showing associated pain (5), some with atypical radiographic appearance (3), some with increased activity on BS (4), some with documented enlargement over time (7), one with abnormal CT attenuation value, some in the setting of osteopoikilosis (2), one in the setting of Gardner's Syndrome and one osteoid osteoma simulating a bone island. This series represents the spectrum of presentations of ABI. Comprehensive review of the literature reveals that the previous largest series of ABI showing enlargement as the atypical feature was in younger patients with jaw BI. Hence, this represents one of the largest series reported of ABI of all types in adults.

Chordoma arising from benign multifocal notochordal tumors.

This case reports a 25-year-old woman initially diagnosed with adjacent benign notochordal cell tumors (BNCTs) of L3 and L4 based on needle biopsy of L3 and stable imaging over a 3-year period who was ultimately found to have a chordoma arising from a BNCT at L3. It illustrates the potential relationship between benign and malignant notochordal tumors and the difficulty in distinguishing them by clinical, radiological, and even histopathological means.

Soft-Tissue Tumors: A Pictorial- and Case-Based Guide to Diagnosis and Management.

General orthopaedic surgeons must learn how to appropriately evaluate patients with soft-tissue masses who present at their office. Although the incidence of benign soft-tissue sarcomas substantially outnumbers that of malignant soft-tissue sarcomas, the mismanagement of soft-tissue tumors markedly increases a patient's morbidity. The appropriate use of imaging modalities helps general orthopaedic surgeons accurately diagnose a soft-tissue mass, initiate appropriate management of a soft-tissue mass, and gain a better understanding of which patients with soft-tissue lesions should be referred to an orthopaedic oncologist.

Peri-Implant Distribution of Polyethylene Debris in Postmortem-Retrieved Knee Arthroplasties: Can Polyethylene Debris Explain Loss of Cement-Bone Interlock in Successful Total Knee Arthroplasties?

BACKGROUND: Loss of mechanical interlock between cement and bone with in vivo service has been recently quantified for functioning, nonrevised, cemented total knee arthroplasties (TKAs). The cause of interlocking trabecular resorption is not known. The goal of this study is to quantify the distribution of PE debris at the cement-bone interface and determine if polyethylene (PE) debris is locally associated with loss of interlock. METHODS: Fresh, nonrevised, postmortem-retrieved TKAs (n = 8) were obtained en bloc. Laboratory-prepared constructs (n = 2) served as negative controls. The intact cement-bone interface of each proximal tibia was embedded in Spurr's resin, sectioned, and imaged under polarized light to identify birefringent PE particles. PE wear particle number density was quantified at the cement-bone interface and distal to the interface, and then compared with local loss of cement-bone interlock. RESULTS: The average PE particle number density for postmortem-retrieved TKAs ranged from 8.6 (1.3) to 24.9 (3.1) particles/mm2 (standard error) but was weakly correlated with years in service. The average particle number density was twice as high as distal (>5mm) to the interface compared to at the interface. The local loss of interlock at the interface was not related to the presence, absence, or particle density of PE. CONCLUSION: PE debris can migrate extensively along the cement-bone interface of well-fixed tibial components. However, the amount of local bone loss at the cement-bone interface was not correlated with the amount of PE debris at the interface, suggesting that the observed loss of trabecular interlock in these well-fixed TKAs may be due to alternative factors.

Parathyroid Hormone (1-34) Transiently Protects Against Radiation-Induced Bone Fragility.

Radiation therapy for soft tissue sarcoma or tumor metastases is frequently associated with damage to the underlying bone. Using a mouse model of limited field hindlimb irradiation, we assessed the ability of parathyroid hormone (1-34) fragment (PTH) delivery to prevent radiation-associated bone damage, including loss of mechanical strength, trabecular architecture, cortical bone volume, and mineral density. Female BALB/cJ mice received four consecutive doses of 5 Gy to a single hindlimb, accompanied by daily injections of either PTH or saline (vehicle) for 8 weeks, and were followed for 26 weeks. Treatment with PTH maintained the mechanical strength of irradiated femurs in axial compression for the first eight weeks of the study, and the apparent strength of irradiated femurs in PTH-treated mice was greater than that of naïve bones during this time. PTH similarly protected against radiation-accelerated resorption of trabecular bone and transient decrease in mid-diaphyseal cortical bone volume, although this benefit was maintained only for the duration of PTH delivery. Overall, PTH conferred protection against radiation-induced fragility and morphologic changes by increasing the quantity of bone, but only during the period of administration. Following cessation of PTH delivery, bone strength and trabecular volume fraction rapidly decreased. These data suggest that PTH does not negate the longer-term potential for osteoclastic bone resorption, and therefore, finite-duration treatment with PTH alone may not be sufficient to prevent late onset radiotherapy-induced bone fragility.

Image intensive soft tissue sarcoma surveillance uncovers pathology earlier than patient complaints but with frequent initially indeterminate lesions.

INTRODUCTION: Post-treatment surveillance follow-up soft-tissue sarcomas is controversial. Protocols are highly variable. This study retrospectively evaluates an image intense protocol to assess benefits of identifying true pathology compared to incidental findings. METHODS: A retrospective chart review was conducted on a single orthopedic oncologist's soft tissue sarcoma patients under a consistent protocol (TAD). Study population included patients who underwent resection of non-metastatic soft tissue sarcoma (AJCC stages I-III) and either died within surveillance period or completed 5 years of follow-up. RESULTS: Thirty-nine patients met the strict study criteria. 24/39 (61.5%) patients were identified to have a local recurrence (6), chest metastasis (6), isolated distant recurrence (9), or new primary tumor (3). Of those 24 patients with true pathology, 13 (54%) or 33% (13/39) of all patients potentially benefited from discovery via imaging before patient complaint. Chest CT was the first to reveal all lung metastases. For balance, 32/39 (82%) patients had at least 1 initially "indeterminate" lesion on imaging. Of those, 91% (29/32)-74% of all patients (29/39)-proved to be inconsequential by final follow up. CONCLUSION: Of the true pathology identified, over half were not evident on clinical presentation, emphasizing the importance of a routine surveillance. However, an image intense surveillance program has a high rate of initially indeterminate findings. J. Surg. Oncol. 2016;113:818-822. © 2016 Wiley Periodicals, Inc.

Does CT-based Rigidity Analysis Influence Clinical Decision-making in Simulations of Metastatic Bone Disease?

BACKGROUND: There is a need to improve the prediction of fracture risk for patients with metastatic bone disease. CT-based rigidity analysis (CTRA) is a sensitive and specific method, yet its influence on clinical decision-making has never been quantified. QUESTIONS/PURPOSES: What is the influence of CTRA on providers' perceived risk of fracture? (2) What is the influence of CTRA on providers' treatment recommendations in simulated clinical scenarios of metastatic bone disease of the femur? (3) Does CTRA improve interobserver agreement regarding treatment recommendations? METHODS: We conducted a survey among 80 academic physicians (orthopaedic oncologists, musculoskeletal radiologists, and radiation oncologists) using simulated vignettes of femoral lesions presented as three separate scenarios: (1) no CTRA input (baseline); (2) CTRA input suggesting increased risk of fracture (CTRA+); and (3) CTRA input suggesting decreased risk of fracture (CTRA-). Participants were asked to rate the patient's risk of fracture on a scale of 0% to 100% and to provide a treatment recommendation. Overall response rate was 62.5% (50 of 80). RESULTS: When CTRA suggested an increased risk of fracture, physicians perceived the fracture risk to be slightly greater (37% ± 3% versus 42% ± 3%, p < 0.001; mean difference [95% confidence interval {CI}] = 5% [4.7%-5.2%]) and were more prone to recommend surgical stabilization (46% ± 9% versus 54% ± 9%, p < 0.001; mean difference [95% CI] = 9% [7.9-10.1]). When CTRA suggested a decreased risk of fracture, physicians perceived the risk to be slightly decreased (37% ± 25% versus 35% ± 25%, p = 0.04; mean difference [95% CI] = 2% [2.74%-2.26%]) and were less prone to recommend surgical stabilization (46% ± 9% versus 42% ± 9%, p < 0.03; mean difference [95% CI] = 4% [3.9-5.1]). The effect size of the influence of CTRA on physicians' perception of fracture risk and treatment planning varied with lesion severity and specialty of the responders. CTRA did not increase interobserver agreement regarding treatment recommendations when compared with the baseline scenario (κ = 0.41 versus κ = 0.43, respectively). CONCLUSIONS: Based on this survey study, CTRA had a small influence on perceived fracture risk and treatment recommendations and did not increase interobserver agreement. Further work is required to properly introduce this technique to physicians involved in the care of patients with metastatic lesions. Given the number of preclinical and clinical studies outlining the efficacy of this technique, better education through presentations at seminars/webinars and symposia will be the first step. This should be followed by clinical trials to establish CTRA-based clinical guidelines based on evidence-based medicine. Increased exposure of clinicians to CTRA, including its underlying methodology to study bone structural characteristics, may establish CTRA as a uniform guideline to assess fracture risk. LEVEL OF EVIDENCE: Level III, economic and decision analyses.

CT-based Structural Rigidity Analysis Is More Accurate Than Mirels Scoring for Fracture Prediction in Metastatic Femoral Lesions.

BACKGROUND: Controversy continues regarding the appropriate assessment of fracture risk in long bone lesions affected by disseminated malignancy. QUESTIONS/PURPOSES: The purpose of this ongoing Musculoskeletal Tumor Society-sponsored, multi-institutional prospective cross-sectional clinical study is to compare CT-based structural rigidity analysis (CTRA) with physician-derived Mirels scoring for predicting pathologic fracture in femoral bone lesions. We hypothesized CTRA would be superior to Mirels in predicting fracture risk within the first year based on (1) sensitivity, specificity, positive predictive value, and negative predictive value; (2) receiver operator characteristic (ROC) analysis; and (3) fracture prediction after controlling for potential confounding variables such as age and lesion size. METHODS: Consented patients with femoral metastatic lesions were assigned Mirels scores by the individual enrolling orthopaedic oncologist based on plain radiographs and then underwent CT scans of both femurs with a phantom of known density. The CTRA was then performed. Between 2004 and 2008, six study centers performed CTRA on 125 patients. The general indications for this test were femoral metastatic lesions potentially at risk of fracture. The enrolling physician was allowed the choice of prophylactic stabilization or nonsurgical treatment, and the local treating oncology team along with the patient made this decision. Of those 125 patients, 78 (62%) did not undergo prophylactic stabilization and had followup sufficient for inclusion, which was fracture through the lesion within 12 months of CTRA, death within 12 months of CTRA, or 12-month survival after CTRA without fracture, whereas 15 (12%) were lost to followup and could not be studied here. The mean patient age was 61 years (SD, 14 years). There were 46 women. Sixty-four of the lesions were located in the proximal femur, 13 were in the diaphysis, and four were distal. Osteolytic lesions prevailed (48 lesions) over mixed (31 lesions) and osteoblastic (15 lesions). The most common primary cancers were breast (25 lesions), lung (14 lesions), and myeloma (11 lesions). CTRA was compared with Mirels based on sensitivity/specificity analysis, ROC, and fracture prediction by multivariate analysis. For the CTRA, reduction greater than 35% in axial, bending, or torsional rigidities at the lesion was considered at risk for fracture, whereas a Mirels score of 9 or above, as suggested in the original manuscript, was used as the definition of impending fracture. RESULTS: CTRA provided higher sensitivity (100% versus 66.7%), specificity (60.6% versus 47.9%), positive predictive value (17.6% versus 9.8%), and negative predictive value (100% versus 94.4%) compared with the classic Mirels definition of impending fracture (≥ 9), although there was considerable overlap in the confidence intervals. ROC curve analysis found CTRA to be better than the Mirels score regardless of what Mirels score cutoff was used. After controlling for potential confounding variables including age, lesion size, and Mirels scores, multivariable logistic regression indicated that CTRA was a better predictor of fracture (likelihood ratio test = 10.49, p < 0.001). CONCLUSIONS: CT-based structural rigidity analysis is better than Mirels score in predicting femoral impending pathologic fracture. CTRA appears to provide a substantial advance in the accuracy of predicting pathological femur fracture over currently used clinical and radiographic criteria. LEVEL OF EVIDENCE: Level III, diagnostic study.