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.

Denosumab administration for bone metastases from solid tumors: a retrospective cross-sectional study.

BACKGROUND: Little is known on how denosumab reduces skeletal-related events (SREs) by bone metastases from solid tumors. We sought to evaluate the effect of denosumab administration in patients with bone metastases from solid tumors. METHODS: Data of patients treated with denosumab were collected from electronic medical charts (n = 496). Eligible participants in this study were adult patients (age ≥ 18 years) with metastatic bone lesions from solid tumors treated with denosumab. SREs, surgical interventions, the spinal instability neoplastic score (SINS) for spinal region, and Mirels' score for the appendicular region were evaluated. To assess whether denosumab could prevent SREs and associated surgery, the SINS and Mirels' score were compared between patients with and without SREs. RESULTS: A total of 247 patients (median age, 65.5 years old; median follow-up period, 13 months) treated with denosumab for metastatic bone lesions from solid tumors were enrolled in this study. SREs occurred in 19 patients (7.7%). SREs occurred in 2 patients (0.8%) who took denosumab administration before SREs. Surgical interventions were undertaken in 14 patients (5.7%) (spinal and intradural lesions in five patients and appendicular lesions in nine patients). The mean SINS of patients without SREs compared to those with SREs were 7.5 points and 10.2 points, respectively. The mean Mirels' scores of non-SREs patients and those with SREs were 8.07 points and 10.7 points, respectively. Patients with SREs had significantly higher Mirels' score than non-SREs patients (p < 0.01). Patients with SREs had higher SINS than non-SREs patients (p = 0.09). CONCLUSIONS: SREs occurred in patients with higher SINS or Mirels' scores. Two patients suffered from SREs though they took denosumab administration before SREs. Appropriate management of denosumab for patients with bone metastasis is significant. Surgical interventions may be needed for patients who with higher SINS or Mirel's scores.

A precision-based exercise program for patients with multiple myeloma.

OBJECTIVES: Aim of this study was to retrospectively evaluate an interdisciplinary consultation followed by a precision-based exercise program (PEP) for myeloma patients with stable and unstable bone lesions. METHODS: Data of myeloma patients (n = 100) who received a PEP according to an orthopedic evaluation were analyzed. Bone stability was assessed by established scoring systems (Spinal Instability Neoplastic Score [SINS], Mirels' score). All patients with stable and unstable osteolyses received a PEP and n = 91 were contacted for a follow-up interview. RESULTS: In 60% of patients at least one osteolysis of the spine was considered potentially unstable or unstable. Following consultation, the number of patients performing resistance training could be significantly increased (≥2 sessions/week, 55%). Musculoskeletal pain was reported frequently. At the follow-up interview, 75% of patients who performed PEP stated that painful symptoms could be effectively alleviated by exercise. Moreover, only patients who exercised regularly discontinued pain medication. No injuries were reported in association with PEP. CONCLUSION: We were able to demonstrate that individualized resistance training is implementable and safe for myeloma patients. By means of a PEP, patients' self-efficacy in managing musculoskeletal pain was enhanced and pain medication could be reduced.

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.

Chemotherapy May Obviate Prophylactic Femoral Nail Surgery for Multiple Myeloma Patients With High Mirels' Score Lesions and Impending Pathological Hip Fracture.

Bone involvement presents in >80% of patients with multiple myeloma. This causes lytic lesions for which prophylactic surgery is indicated to prevent pathological fractures if the lesion is graded ≥9/12 on Mirels' score. Although successful, these surgeries have risks and extended recovery periods. We present a case indicating myeloma chemotherapy may obviate prophylactic femoral nailing for high Mirels' score lesions in the femoral head with impending pathological hip fracture. A 72-year-old woman presented in December 2017 with back pain. A plain X-ray indicated degenerative anterolisthesis in her lumbosacral spine. Serum analysis revealed abnormal protein, globulin, alkaline phosphatase, and albumin levels while protein electrophoresis and serum immunofixation revealed raised immunoglobulin A (IgA) kappa paraprotein and kappa serum free light chains, respectively. Whole-body CT scans showed widespread lytic bone lesions and bone marrow biopsy confirmed infiltration by plasma cells. She was diagnosed with International Staging System (ISS) stage 3 multiple myeloma, which was successfully treated with bortezomib, thalidomide and dexamethasone with regular bisphosphonates that year. She presented again to the hospital in June 2020 with acute back and pelvic pain; Her paraprotein and serum-free light chains had increased significantly from her previous clinic appointment, indicating serological progression. MRI showed a relapse of the myeloma deposits in her right femoral head and spine. The deposit in her femoral head was graded 10/12 on Mirels' score, which indicated prophylactic femoral nailing. Instead, the patient was treated with daratumumab, bortezomib, and dexamethasone with escalation to monthly zoledronic acid infusions, as it was thought surgery would provide limited cytoreductive effect, preventing chemotherapy for six weeks post-surgery, potentiating pathological hip fracture and disease progression at other sites. This resulted in a complete response, thus reducing the deposits such that the femoral lesion was graded <8 on Mirels' score, improved her pain, and restored her ability to traverse stairs. She remains in complete response with ongoing daratumumab and denosumab maintenance treatment as of December 2022. Chemotherapy and bisphosphonates substantially reduced the myeloma deposit in the femoral head such that indications of prophylactic surgery were eliminated according to Mirels' score recommendations. This reduced the risk of pathological hip fracture whilst eliminating surgical complications. Further research should be conducted into the safety and efficacy of this treatment regimen in patients with high Mirels' score lesions. With this knowledge, consideration can be taken as to whether prophylactic femoral nailing is necessary given strong indications.

Mirels' score for upper limb metastatic lesions: do we need a different cutoff for recommending prophylactic fixation?

Hypothesis: The aim of this study was to investigate the reproducibility, reliability, and accuracy of Mirels' score in upper limb bony metastatic disease and validate its use in predicting pathologic fractures. Methods: Forty-five patients with upper limb bony metastases met the inclusion criteria (62% male 28/45). The mean age was 69 years (SD 9.5), and the most common primaries were lung (29%, 13/45), followed by prostate and hematological (each 20%, 9/45). The most commonly affected bone was the humerus (76%, 35/45), followed by the ulna (6.5%, 3/45). Mirels' score was calculated in 32 patients; with plain radiographs at index presentation scored using Mirels' system by 6 raters. The radiological aspects (lesion size and appearance) were scored twice by each rater (2 weeks apart). Intraobserver and interobserver reliability were calculated using Fleiss' kappa test. Bland-Altman plots compared the variances of both individual components and the total Mirels' score. Results: The overall fracture rate of upper limb metastatic lesions was 76% (35/46) with a mean follow-up of 3.6 years (range 11 months-6.8 years). Where time from diagnosis to fracture was known (n = 20), fractures occurred at a median 19 days (interquartile range 60-10), and 80% (16/20) occurred within 3 months of diagnosis.Mirels' score of ≥9 did not accurately predict lesions that fractured (fracture rate 11%, 5/46, for Mirels' ≥ 9 vs. 65%, 30/46, for Mirels' ≤ 8, P < .001). Sensitivity was 14%, and specificity was 73%. When Mirels' cutoff was lowered to ≥7, patients were more likely to fracture than not (48%, 22/46, vs. 28%, 13/46, P = .045); sensitivity rose to 63%, but specificity fell to 55%.Kappa values for interobserver variability were κ = 0.358 (fair, 95% confidence interval [CI] 0.288-0.429) for lesion size, κ = 0.107 (poor, 95% CI 0.02-0.193) for radiological appearance, and κ = 0.274 (fair, 95% CI 0.229-0.318) for total Mirels' score. Values for intraobserver variability were κ = 0.716 (good, 95% CI 0.432-0.999) for lesion size, κ = 0.427 (moderate, 95% CI 0.195-0.768) for radiological appearance, and κ = 0.580 (moderate, 95% CI 0.395-0.765) for total Mirels' score. Conclusions: This study demonstrates moderate to substantial agreement between and within raters using Mirels' score on upper limb radiographs. However, Mirels' score had a poor sensitivity and specificity in predicting upper extremity fractures. Until a more valid scoring system has been developed, based on our study, we recommend a Mirels' threshold of ≥7/12 for considering prophylactic fixation of impending upper limb pathologic fractures. This contrasts with the current ≥9/12 cutoff, which is recommended for lower limb pathologic fractures.

Effectiveness of Rehabilitation for Cancer Patients with Bone Metastasis.

Objectives: Advances in cancer treatment have led to extended survival, and, as a result, the number of patients with bone metastases is increasing. Activities of daily living (ADL) decrease with bone metastasis and the need for rehabilitation is increasing. This study examined the effects of rehabilitation in patients with bone metastases. Methods: We retrospectively reviewed data of cancer patients with bone metastasis who received rehabilitation between 2016 and 2018. Efficacy of rehabilitation was evaluated in 92 patients as the change in the Functional Independence Measure (FIM) score divided by rehabilitation days (FIM change/day) and assessed by different metastatic sites. Results: Overall FIM scores significantly improved after rehabilitation. Moreover, FIM change/day improved in patients with pelvic metastases (n=44) more than in patients with other metastatic sites (n=48) (P=0.015). In FIM motor components, improvements in toilet, tub/shower, walk/wheelchair, and stairs were significantly greater in patients with pelvic metastasis than in those with other metastasis sites. Conclusions: Rehabilitation improved ADL status to a greater extent in patients with pelvic metastases than in those with other metastasis sites. Patients with pelvic metastases may fear fractures, limiting their ADL, but rehabilitation could eliminate this fear and improve FIM.

Fracture Risk Evaluation of Bone Metastases: A Burning Issue.

Major progress has been achieved to treat cancer patients and survival has improved considerably, even for stage-IV bone metastatic patients. Locomotive health has become a crucial issue for patient autonomy and quality of life. The centerpiece of the reflection lies in the fracture risk evaluation of bone metastasis to guide physician decision regarding physical activity, antiresorptive agent prescription, and local intervention by radiotherapy, surgery, and interventional radiology. A key mandatory step, since bone metastases may be asymptomatic and disseminated throughout the skeleton, is to identify the bone metastasis location by cartography, especially within weight-bearing bones. For every location, the fracture risk evaluation relies on qualitative approaches using imagery and scores such as Mirels and spinal instability neoplastic score (SINS). This approach, however, has important limitations and there is a need to develop new tools for bone metastatic and myeloma fracture risk evaluation. Personalized numerical simulation qCT-based imaging constitutes one of these emerging tools to assess bone tumoral strength and estimate the femoral and vertebral fracture risk. The next generation of numerical simulation and artificial intelligence will take into account multiple loadings to integrate movement and obtain conditions even closer to real-life, in order to guide patient rehabilitation and activity within a personalized-medicine approach.

High rate of fracture in long-bone metastasis: Proposal for an improved Mirels predictive score.

INTRODUCTION: Pathologic fracture is the most feared complication in long-bone metastasis. Various radiographic tools are available for identifying at-risk patients and guide preventive treatment. The Mirels score is the most frequently studied and widely used, but has been criticized, many patients not being operated on until the actual fracture stage. We therefore conducted a French national multicenter prospective study: (1) to determine the proportion of patients operated on at fracture stage versus preventively; (2) to compare Mirels score between the two; and (3) to identify factors for operation at fracture stage according to Mirels score and other epidemiological, clinical and biological criteria. HYPOTHESIS: Simple discriminatory items can be identified to as to complete the Mirels score and enhance its predictive capacity. MATERIAL AND METHODS: A non-controlled multicenter prospective study included 245 patients operated on for non-revelatory long-bone metastasis, comparing patients operated on for fracture versus preventively according to body-mass index (BMI), ASA score, Katagiri score items and the 4 Mirels items. RESULTS: One hundred and twenty-six patients (51.4%) were operated on at fracture stage: 106 (84.1%) showed high risk on Mirels score (score>8), and 15 (11.9%) moderate risk (score=8). On multivariate analysis, 4 independent factors emerged: in increasing order, advanced age (OR=1.03; 95%CI 1.01-1.06), VAS pain score>6 (OR=1.47; 95%CI 1.02-2.11), WHO grade>2 (OR=2.74; 95%CI 1.22-6.15), and upper-limb location (OR=5.26; 95%CI 2.13-12.84). DISCUSSION: The present study confirmed that more than half of patients with long-bone metastasis are operated on at actual fracture stage, in agreement with the literature. Several studies highlighted the weakness of the Mirels score as a predictive instrument. Comparison between preventive and fracture-stage surgery showed that upper-limb location, intense pain, advanced age and impaired functional status were associated with fracture-stage surgery, and should be taken into account alongside the original Mirels criteria. This improved scoring instrument remains to be validated in a prospective study. LEVEL OF EVIDENCE: IV, prospective cohort study without control group.

The validity of the Mirels score for predicting impending pathological fractures of the lower limb.

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.

The insufficiencies of risk analysis of impending pathological fractures in patients with femoral metastases: A literature review.

PURPOSE: Pathologic fractures in patients with bone metastases are a common problem in clinical orthopaedic routine. On one hand recognition of metastatic lesions, which are at a high risk of fracture, is essential for timely prophylactic fixation, while on the other hand patients with a low risk of pathologic fractures should be spared from overtreatment. The purpose of this review is to identify all methods for fracture risk evaluation in patients with femoral metastases in the literature and to evaluate their predictive values in clinical applications. METHODS: A MEDLINE database literature research was conducted in order to identify clinical scoring systems, conclusions from prospective and retrospective radiologic and/or clinical studies, as well as data from biomechanical experiments, numerical computational methods, and computer simulations. RESULTS: The search identified 441 articles of which 18 articles met the inclusion criteria; 4 more articles were identified from citations of the primarily found studies. In principle there are two distinct methodologies, namely fracture risk prediction factors based on clinical and radiological data such as the most deployed the Mirels' score and fracture risk prediction based on engineering methods. Fracture risk prediction using Mirels' score, based on pure clinical data, shows a negative predictive value between 86 and 100%, but moderate to poor results in predicting non-impending fractures with a positive predictive value between 23 and 70%. Engineering methods provide a high accuracy (correlation coefficient between ex vivo and results from numerical calculations: 0.68 < r2 < 0.96) in biomechanical lab experiments, but have not been applied to clinical routine yet. CONCLUSION: This review clearly points out a lack of adequate clinical methods for fracture risk prediction in patients with femoral metastases. Today's golden standard, the Mirels' score leads to an overtreatment. Whereas, engineering methods showed high potential but require a clinical validation. In future definition of patient-specific, quantitative risk factor based modelling methods could serve as useful decision support for individualized treatment strategies in patients with a metastatic lesion.

Simulating activities of daily living with finite element analysis improves fracture prediction for patients with metastatic femoral lesions.

Predicting fracture risk for patients with metastatic femoral lesions remains an important clinical problem. Mirels' criterion remains the most formalized radiographic scoring system with good sensitivity (correctly identifying clinical fractures) but relatively poor specificity (correctly identify cases that do not fracture). A series of patients with metastatic femoral lesions had Computed Tomography (CT) scans, were followed prospectively for 4 months, and categorized into fracture (n = 5), non-fracture (n = 28), or stabilized (n = 11) groups. CT based-Finite Element (FE) modeling was used to predict fracture for these cases using axial compression (AC), level walking (LW), and aggressive stair ascent (ASA) loading conditions. The FE predicted fracture force was greater for the non-fracture compared to the fracture group for all loading cases. The ability of the FE models to predict fracture cases (sensitivity) was similar for the groups (Mirels, AC, LW: 80%, ASA: 100%). The ability of the models to correctly predict the non-fracture cases (specificity) was improved for AC (71%) and LW (86%) loading conditions, when compared to Mirels specificity (43%), but poorer for the ASA (21%) conditions. The results suggest that FE models that assess fracture risk using LW conditions can improve fracture prediction over Mirels scoring in a clinical population.