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

Timothy A. Damron, Ara Nazarian, Vahid Entezari, Carlos Brown, William Grant, Nathan Calderon, David Zurakowski, Richard M. Terek, Megan E. Anderson, Edward Y. Cheng, Albert J. Aboulafia, Mark C. Gebhardt, Brian D. Snyder

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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.

Original languageEnglish (US)
Pages (from-to)643-651
Number of pages9
JournalClinical orthopaedics and related research
Issue number3
StatePublished - Mar 1 2016

Bibliographical note

Funding Information:
We thank John A. Hipp PhD, who was integral in the development of the CTRA technique, Felix Cheung MD, Patrick Lin MD, and Robert Turcotte MD, who were active in getting the study through the institutional review board at their respective institutions, and the members of the Musculoskeletal Tumor Society and its leadership for the initial and ongoing support of this multiinstitutional study in part through contributions to the Orthopaedic Education and Research Foundation. This study has been partially funded by a grant from the Musculoskeletal Tumor Society (co-Principal Investigators TAD and BDS) and grants from the Carol Baldwin Breast Cancer Research Foundation (TAD), Boston Children's Hospital Orthopaedic Surgery Foundation (BDS) and the National Institutes of Health (NIH T32 COMET Program (AN: AR055885) and NIH-LRP (AN: L30 AR056606).

Publisher Copyright:
© 2015, The Association of Bone and Joint Surgeons®.


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