M. Matzinger

Advanced Vertebral Fracture among Newly Diagnosed Children with Acute Lymphoblastic Leukemia: Results of the Canadian STeroid-associated Osteoporosis in the Pediatric Population (STOPP) Research Program

Vertebral compression is a serious complication of childhood acute lymphoblastic leukemia (ALL). The prevalence and pattern of vertebral fractures, as well as their relationship to BMD and other clinical indices, have not been systematically studied. We evaluated spine health in 186 newly diagnosed children (median age, 5.3 yr; 108 boys) with ALL (precursor B cell: N = 167; T cell: N = 19) who were enrolled in a national bone health research program. Patients were assessed within 30 days of diagnosis by lateral thoraco‐lumbar spine radiograph, bone age (also used for metacarpal morphometry), and BMD. Vertebral morphometry was carried out by the Genant semiquantitative method. Twenty‐nine patients (16%) had a total of 75 grade 1 or higher prevalent vertebral compression fractures (53 thoracic, 71%; 22 lumbar). Grade 1 fractures as the worst grade were present in 14 children (48%), 9 patients (31%) had grade 2 fractures, and 6 children (21%) had grade 3 fractures. The distribution of spine fracture was bimodal, with most occurring in the midthoracic and thoraco‐lumbar regions. Children with grade 1 or higher vertebral compression had reduced lumbar spine (LS) areal BMD Z‐scores compared with those without (mean ± SD, −2.1 ± 1.5 versus −1.1 ± 1.2; p < 0.001). LS BMD Z‐score, second metacarpal percent cortical area Z‐score, and back pain were associated with increased odds for fracture. For every 1 SD reduction in LS BMD Z‐score, the odds for fracture increased by 80% (95% CI: 10–193%); the presence of back pain had an OR of 4.7 (95% CI: 1.5–14.5). These results show that vertebral compression is an under‐recognized complication of newly diagnosed ALL. Whether the fractures will resolve through bone growth during or after leukemia chemotherapy remains to be determined.

Prevalent Vertebral Fractures among Children Initiating Glucocorticoid Therapy for the Treatment of Rheumatic Disorders

Vertebral fractures are an under‐recognized problem in children with inflammatory disorders. We studied spine health among 134 children (87 girls) with rheumatic conditions (median age 10 years) within 30 days of initiating glucocorticoid therapy.

Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study.

To determine the frequency of incident vertebral fractures (IVF) 12 months after glucocorticoid (GC) initiation in children with rheumatic diseases and to identify children at higher risk.

High Incidence of Vertebral Fractures in Children With Acute Lymphoblastic Leukemia 12 Months After the Initiation of Therapy

PURPOSE Vertebral fractures due to osteoporosis are a potential complication of childhood acute lymphoblastic leukemia (ALL). To date, the incidence of vertebral fractures during ALL treatment has not been reported. PATIENT AND METHODS We prospectively evaluated 155 children with ALL during the first 12 months of leukemia therapy. Lateral thoracolumbar spine radiographs were obtained at baseline and 12 months. Vertebral bodies were assessed for incident vertebral fractures using the Genant semiquantitative method, and relevant clinical indices such as spine bone mineral density (BMD), back pain, and the presence of vertebral fractures at baseline were analyzed for association with incident vertebral fractures. RESULTS Of the 155 children, 25 (16%; 95% CI, 11% to 23%) had a total of 61 incident vertebral fractures, of which 32 (52%) were moderate or severe. Thirteen (52%) of the 25 children with incident vertebral fractures also had fractures at baseline. Vertebral fractures at baseline increased the odds of an incident fracture at 12 months by an odds ratio of 7.3 (95% CI, 2.3 to 23.1; P = .001). In addition, for every one standard deviation reduction in spine BMD Z-score at baseline, there was 1.8-fold increased odds of incident vertebral fracture at 12 months (95% CI, 1.2 to 2.7; P = .006). CONCLUSION Children with ALL have a high incidence of vertebral fractures after 12 months of chemotherapy, and the presence of vertebral fractures and reductions in spine BMD Z-scores at baseline are highly associated clinical features.

Reliability Assessment of Society for Fetal Urology Ultrasound Grading System for Hydronephrosis

PURPOSE The Society for Fetal Urology introduced a subjective grading system for classifying hydronephrosis that has important implications in patient diagnosis, treatment and outcome. The grading system is frequently used to standardize the severity of hydronephrosis, and compare results among patients and centers. Despite widespread use to our knowledge no groups have investigated the reliability of the grading system since its introduction. We assessed the intrarater and interrater reliability of the Society for Fetal Urology grading system for hydronephrosis and examined levels of agreement by the degree of hydronephrosis (grades 0 to 4) and level of experience (staff vs trainee). MATERIALS AND METHODS A series of 50 pediatric renal ultrasound images from patients with a diagnosis of hydronephrosis were assessed by 4 staff individuals and 4 trainees using the Society for Fetal Urology grading system. Ultrasound images included the kidneys, ureters and bladder to be consistent with practice. After 7 to 14 days each rater repeated the assessment. The nonweighted Cohen kappa statistic was used to estimate intrarater and interrater reliability by Society for Fetal Urology grade and training level. RESULTS Staff and trainee raters independently assigned Society for Fetal Urology grades to 50 patients (99 renal units). The average number of images per ultrasound was 41, including the right and left kidneys. Overall interrater agreement for staff individuals was substantial for grade 0, moderate for grades 1, 2 and 4, and only slight to fair for grade 3. Intrarater agreement was substantial to almost perfect for staff agreement (range 69% to 94%, kappa 0.56 to 0.89) and trainees (range 63% to 90%, kappa 0.48 to 0.85). CONCLUSIONS Our study suggests that the Society for Fetal Urology grading system has good intrarater but modest interrater reliability. Individual rater interpretations of the grading system may explain the modest interrater agreement. Proposed modifications to the Society for Fetal Urology classification system, such as distinguishing between diffuse and segmental cortical thinning, may improve reliability.

The choice of normative pediatric reference database changes spine bone mineral density Z-scores but not the relationship between bone mineral density and prevalent vertebral fractures.

OBJECTIVES Our objectives were to assess the magnitude of the disparity in lumbar spine bone mineral density (LSBMD) Z-scores generated by different reference databases and to evaluate whether the relationship between LSBMD Z-scores and vertebral fractures (VF) varies by choice of database. PATIENTS AND DESIGN Children with leukemia underwent LSBMD by cross-calibrated dual-energy x-ray absorptiometry, with Z-scores generated according to Hologic and Lunar databases. VF were assessed by the Genant method on spine radiographs. Logistic regression was used to assess the association between fractures and LSBMD Z-scores. Net reclassification improvement and area under the receiver operating characteristic curve were calculated to assess the predictive accuracy of LSBMD Z-scores for VF. RESULTS For the 186 children from 0 to 18 years of age, 6 different age ranges were studied. The Z-scores generated for the 0 to 18 group were highly correlated (r ≥ 0.90), but the proportion of children with LSBMD Z-scores ≤-2.0 among those with VF varied substantially (from 38-66%). Odds ratios (OR) for the association between LSBMD Z-score and VF were similar regardless of database (OR = 1.92, 95% confidence interval 1.44, 2.56 to OR = 2.70, 95% confidence interval 1.70, 4.28). Area under the receiver operating characteristic curve and net reclassification improvement ranged from 0.71 to 0.75 and -0.15 to 0.07, respectively. CONCLUSIONS Although the use of a LSBMD Z-score threshold as part of the definition of osteoporosis in a child with VF does not appear valid, the study of relationships between BMD and VF is valid regardless of the BMD database that is used.

Periorbital ecchymosis ("raccoon eyes") on a bone scan.

A 5-month-old girl presented to the emergency room with bilateral periorbital ecchymosis for the past week with no history of trauma. On examination, other than the ecchymosis she was found to have an abdominal mass and hepatomegaly. Workup of the patient showed that she had a left suprarenal mass with metastatic lesions in the liver, as well as bone marrow involvement. Pathology of the lesion showed it to be favorable histology neuroblastoma. The bone scan showed metastatic involvement involving the orbital margins, maxillae, middle cranial fossae, and frontal bones bilaterally (Figure). The patient was classified as stage IV intermediate risk neuroblastoma and treated with chemotherapy.

Incident vertebral fractures 12 months following glucocorticoid initiation in children with rheumatic disorders

Incident vertebral fractures 12 months following glucocorticoid initiation in children with rheumatic disorders Bianca A Lang, Celia Rodd, Timothy Ramsay, David A Cabral, Peter B Dent, Janet E Ellsworth, Kristin M Houghton, Adam Huber, Roman Jurencak, Maggie Larche, Claire MA LeBlanc, Brian Lentle, MaryAnn Matzinger, Paivi M Miettunen, Kiem Oen, Johannes Roth, Claire Saint-Cyr, Rosie Scuccimarri, Nazih Shenouda, Leanne M Ward, Canadian STOPP Consortium