title: CT-based Structural Rigidity Analysis Is More Accurate Than Mirels Scoring for Fracture Prediction in Metastatic Femoral Lesions.
abstract: BACKGROUND
  Controversy continues regarding the appropriate assessment of fracture risk in long bone lesions affected by disseminated malignancy.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  Level III, diagnostic study.
authors.affiliation: Department of Orthopedic Surgery, Upstate Bone and Joint Center, State University of New York Upstate Medical University, 6620 Fly Road, Suite 200, East Syracuse, NY, 13057, USA. damront@upstate.edu.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Damron
authors.affiliation: Department of Orthopaedic Surgery, Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Ara
authors.initials: A
authors.lastname: Nazarian
authors.affiliation: Department of Orthopaedic Surgery, Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Vahid
authors.initials: V
authors.lastname: Entezari
authors.affiliation: Department of Orthopedic Surgery, Upstate Bone and Joint Center, State University of New York Upstate Medical University, 6620 Fly Road, Suite 200, East Syracuse, NY, 13057, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Brown
authors.affiliation: Biostatistics, Department of Emergency Medicine, Upstate Medical University, Syracuse, NY, USA.
authors.forename: William
authors.initials: W
authors.lastname: Grant
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Calderon
authors.affiliation: Departments of Anesthesiology and Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.affiliation: Department of Orthopaedic Surgery, Rhode Island Hospital, Providence, RI, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Terek
authors.affiliation: Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Anderson
authors.affiliation: Department of Orthopaedic Surgery, University of Minnesota Medical Center, Minneapolis, MN, USA.
authors.forename: Edward Y
authors.initials: EY
authors.lastname: Cheng
authors.affiliation: Department of Orthopaedic Surgery, Sinai Hospital, Baltimore, MD, USA.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Aboulafia
authors.affiliation: Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Gebhardt
authors.affiliation: Department of Orthopaedic Surgery, Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Snyder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D005260:Female; D005266:Femoral Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary; D005598:Fractures, Spontaneous / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019047:Phantoms, Imaging; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011859:Radiography; D012680:Sensitivity and Specificity; D016019:Survival Analysis