Risk factors associated with prevalent vertebral fractures in Duchenne muscular dystrophy.

Patients with Duchenne muscular dystrophy (DMD) have a high fracture burden due to progressive myopathy and steroid-induced osteoporosis. This study in males with DMD showed that markers of systemic glucocorticoid exposure including shorter stature, greater bone age delay, and lower lumbar spine bone mineral density were associated with spine fragility. INTRODUCTION: Fragility  fractures are frequent in DMD. The purpose of this study was to identify clinical factors associated with prevalent vertebral fractures (VF) in boys, teens/young adults with Duchenne muscular dystrophy (DMD). METHODS: This was a cross-sectional study of males aged 4-25 years with DMD. VF were evaluated using the modified Genant semi-quantitative method on T4-L4 lateral spine radiographs. Areal bone mineral density (aBMD) was measured at the lumbar spine (LS) and used to estimate volumetric BMD (vBMD). Clinical factors were analyzed for their association with the Spinal Deformity Index (SDI, the sum of the Genant grades). RESULTS: Sixty participants were enrolled (mean age 11.5 years, range 5.4-19.5). Nineteen participants (32%) had a total of 67 VF; 23/67 VF (34%) were moderate or severe. Participants with VF were shorter (mean height Z-score ± standard deviation: - 3.1 ± 1.4 vs. - 1.8 ± 1.4, p = 0.001), had longer glucocorticoid exposure (mean duration 6.0 ± 3.3 vs. 3.9 ± 3.3 years, p = 0.027), greater bone age (BA) delay (mean BA to chronological age difference - 3.2 ± 3.4 vs. - 1.3 ± 1.2 years, p = 0.035), and lower LSaBMD Z-scores (mean - 3.0 ± 1.0 vs. - 2.2 ± 1.2, p = 0.023). There was no difference in LSvBMD Z-scores. Multivariable Poisson regression showed that every 0.1 mg/kg/day increment in average glucocorticoid daily dose was associated with a 1.4-fold SDI increase (95% confidence interval: 1.1-1.7, p = 0.013). Greater BA delay (p < 0.001), higher weight Z-score (p = 0.004), decreased height Z-score (p = 0.025), and lower LSvBMD Z-score (p = 0.025) were also associated with SDI increase. CONCLUSION: Readily measurable clinical variables were associated with prevalent VF in males with glucocorticoid-treated DMD. These variables may be useful to identify candidates for primary osteoporosis prevention after glucocorticoid initiation.

Comparison of Body Composition, Muscle Strength and Cardiometabolic Profile in Children with Prader-Willi Syndrome and Non-Alcoholic Fatty Liver Disease: A Pilot Study.

Syndromic and non-syndromic obesity conditions in children, such as Prader-Willi syndrome (PWS) and non-alcoholic fatty liver disease (NAFLD), both lower quality of life and increase risk for chronic health complications, which further increase health service utilization and cost. In a pilot observational study, we compared body composition and muscle strength in children aged 7−18 years with either PWS (n = 9), NAFLD (n = 14), or healthy controls (n = 16). Anthropometric and body composition measures (e.g., body weight, circumferences, skinfolds, total/segmental composition, and somatotype), handgrip strength, six minute-walk-test (6MWT), physical activity, and markers of liver and cardiometabolic dysfunction (e.g., ALT, AST, blood pressure, glucose, insulin, and lipid profile) were measured using standard procedures and validated tools. Genotyping was determined for children with PWS. Children with PWS had reduced lean body mass (total/lower limb mass), lower handgrip strength, 6MWT and increased sedentary activity compared to healthy children or those with NAFLD (p < 0.05). Children with PWS, including those of normal body weight, had somatotypes consistent with relative increased adiposity (endomorphic) and reduced skeletal muscle robustness (mesomorphic) when compared to healthy children and those with NAFLD. Somatotype characterizations were independent of serum markers of cardiometabolic dysregulation but were associated with increased prevalence of abnormal systolic and diastolic blood pressure Z-scores (p < 0.05). Reduced lean body mass and endomorphic somatotypes were associated with lower muscle strength/functionality and sedentary lifestyles, particularly in children with PWS. These findings are relevant as early detection of deficits in muscle strength and functionality can ensure effective targeted treatments that optimize physical activity and prevent complications into adulthood.

Controversies Surrounding the BMD Reporting Standard for the Determination of 10-Year Absolute Fracture Risk: A Canadian Perspective.

The Canadian Association of Radiologists and Osteoporosis Canada currently endorse a fracture risk prediction tool called CAROC. It has been used in Canada since 2005 with an update in 2010. It is an integral part of bone mineral densitometry reporting across the country. New osteoporosis guidelines from Osteoporosis Canada (OC) are expected in the near future. There has been pressure on radiologists to report fracture risk using an alternative fracture risk prediction platform called FRAX. In addition, OC collaborated in the development of the Canadian FRAX model and has been copromoting both FRAX and CAROC, raising the prospect that new guidelines may seek to replace CAROC with FRAX for fracture risk determination. A number of concerns have been raised about FRAX, including: (1) FRAX has not released its algorithms to the public domain with the consequence that it is impossible to verify results for an individual patient; (2) FRAX has incorrectly claimed that it was developed by the World Health Organization (WHO) and has used this affiliation to promote itself until recently ordered by the WHO to desist; (3) FRAX requires collection of additional clinical information beyond that needed for CAROC, and this patient-reported medical data is prone to substantial error; and (4) despite claims to the contrary, there are no valid studies comparing FRAX to CAROC. We believe it is important that radiologists be aware of these issues in order to provide input into future Technical Standards for Bone Mineral Densitometry Reporting of the Canadian Association of Radiologists.

Deficits in Muscle Strength and Physical Performance Influence Physical Activity in Sarcopenic Children After Liver Transplantation.

Sarcopenia is a muscle disease characterized by reduced skeletal muscle mass (SMM), muscle strength, and physical performance. Reduced SMM has been identified in children after liver transplantation (LT), but no information related to muscle strength/physical performance or lifestyle factors contributing to sarcopenia is available. We hypothesized that sarcopenia, as determined by measures of SMM, muscle strength, and physical performance, is highly prevalent in children after LT and is related to poor diet quality (DQ) and physical inactivity. A cross-sectional study in post-LT children (n = 22) and age-matched healthy controls (n = 47) between the ages of 6 and 18 years examining body composition (dual energy X-ray absorptiometry and multiple skinfold), measures of muscle strength (handgrip, sit-to-stand, and push-ups), physical performance (6-minute walk test and stair climb test), diet (3-day food intake), and physical activity (accelerometer) was conducted. Low muscle strength/physical performance and SMM (SMM z scores ≤-1.5) were defined by values 2 standard deviations below the mean values for age- and sex-matched controls. Sarcopenia occurred in 36% of children who underwent LT, and they had significantly lower scores for muscle strength (sit-to-stand and push-up tests) and physical performance (stair climb test) than controls (P < 0.05). Deficits in physical performance in children with sarcopenia were predominantly revealed by longer stair climbing times (P = 0.03), with no differences in other muscle tests. Low SMM, muscle strength, and physical performance were associated with a lower amount of time spent in fairly and very active physical activity, but no associations with DQ were found. Sarcopenia is highly prevalent in children after LT and is related to lower moderate-to-vigorous physical activity. Development of effective rehabilitation strategies to treat sarcopenia are needed in post-LT children.

Healthy Body Weights With Corticosteroid-free Immunosuppression Is the Best Predictor of Cardiovascular Health in Children After Liver Transplantation.

INTRODUCTION: Cardiometabolic dysregulation (CMD) influences morbidity and mortality risk in adults post-liver transplantation (LTx). CMD is reported in 10% to 25% of pediatric LTx recipients, but no information regarding the longitudinal expression of CMD is available. The study objective was to examine the longitudinal expression of CMD and associations with body composition and growth in children post-LTx. METHODS: A retrospective review was conducted in youth (34 F/30 M) who underwent LTx between 1994 and 2015 at the Stollery Children's Hospital. Primary outcomes included serum markers of CMD (insulin, glucose, hemoglobin A1C [A1C], homeostasis model assessment for insulin resistance [abnormal >3], lipid panel triglycerides, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol) and systolic/diastolic blood pressure (BP: absolute/z scores). RESULTS: Mean (±SD) age, weight z, height z, body mass index z was 9.7 ±â€Š3.4 years (3.5-17.9), 0.26 ±â€Š1.03, 0.017 ±â€Š1.2, and 0.41 ±â€Š1.05, respectively. The majority of children had percentage fat mass, percentage fat-free mass within normal reference ranges. Systolic/diastolic BP was within healthy references ranges in 83.1% and 93.5% of children, respectively. Serum insulin (83.4%) and high-density lipoprotein-cholesterol (43.9%) concentrations were low, with abnormal findings of other laboratory markers found in <5% of participants. Abnormal findings for metabolic parameters were independent of weight z, body mass index z, fat mass, and corticosteroids but were positively related to child's age (>9.7 years) and fat-free mass (total, arms). Insulin levels decreased significantly in the first 4 years post-LTx, but no changes in lipid panel, A1C and glucose were noted over 10 years. CONCLUSIONS: Pediatric LTx recipients with healthy body weights and corticosteroid-free immunosuppression have a low expression of CMD over 10 years.

The Radiology of Vertebral Fractures in Childhood Osteoporosis Related to Glucocorticoid Administration.

A number of unusual conditions cause decreased bone mass and density in children and these may be associated with low-trauma fractures. However, a series of reports have more recently identified that children with chronic disease sustain vertebral fractures (VFs) much more often than had been suspected. The common denominator involved is glucocorticoid (GC) administration, although other factors such as disease activity come into play. This review will focus on the imaging findings in this form of secondary osteoporosis. Spinal fractures in children have been found to correlate with back pain. At the same time, up to 2/3 of children with VFs in the GC-treated setting are asymptomatic, underscoring the importance of routine surveillance in at-risk children. Other predictors of prevalent and incident VFs include GC exposure (average daily and cumulative dose), declines in lumbar spine bone mineral density Z-scores and increases in body mass index Z-scores, as well as increases in disease activity scores. The imaging diagnosis of osteoporotic VFs in children is made differently from that in adults because immature vertebral bodies continue to ossify during growth. Thus, it is not possible to assess the vertebral end plates or periphery until late, as enchondral ossification extends centripetally within the centrum. Diagnosis, therefore, is much more dependent upon changes in shape than on loss of structural integrity, which may have a more prominent diagnostic role in adults. However, children have a unique ability to model (a growth-dependent process) and thereby reshape previously fractured vertebral bodies. If the underlying disease is successfully treated and the child has sufficient residual growth potential, this means that, on one hand, treatment of the bone disease may be of more limited duration, and, as a last recourse, the diagnosis may be apparent retrospectively.

Performance results for a workstation-integrated radiology peer review quality assurance program.

OBJECTIVE: To assess review completion rates, RADPEER score distribution, and sources of disagreement when using a workstation-integrated radiology peer review program, and to evaluate radiologist perceptions of the program. DESIGN: Retrospective review of prospectively collected data. SETTING: Large private outpatient radiology practice. PARTICIPANTS: Radiologists (n = 66) with a mean of 16.0 (standard deviation, 9.2) years of experience. INTERVENTIONS: Prior studies and reports of cases being actively reported were randomly selected for peer review using the RADPEER scoring system (a 4-point scale, with a score of 1 indicating agreement and scores of 2-4 indicating increasing levels of disagreement). MAIN OUTCOME MEASURES: Assigned peer review completion rates, review scores, sources of disagreement and radiologist survey responses. RESULTS: Of 31 293 assigned cases, 29 044 (92.8%; 95% CI 92.5-93.1%) were reviewed. Discrepant scores (score = 2, 3 or 4) were given in 0.69% (95% CI 0.60-0.79%) of cases and clinically significant discrepancy (score = 3 or 4) was assigned in 0.42% (95% CI 0.35-0.50%). The most common cause of disagreement was missed diagnosis (75.2%; 95% CI 66.8-82.1%). By anonymous survey, 94% of radiologists felt that peer review was worthwhile, 90% reported that the scores they received were appropriate and 78% felt that the received feedback was valuable. CONCLUSION: Workstation-based peer review can increase completion rates and levels of radiologist acceptance while producing RADPEER scores similar to those previously reported. This approach may be one way to increase radiologist engagement in peer review quality assurance.

Common normal variants of pediatric vertebral development that mimic fractures: a pictorial review from a national longitudinal bone health study.

Children with glucocorticoid-treated illnesses are at risk for osteoporotic vertebral fractures, and growing awareness of this has led to increased monitoring for these fractures. However scant literature describes developmental changes in vertebral morphology that can mimic fractures. The goal of this paper is to aid in distinguishing between normal variants and fractures. We illustrate differences using lateral spine radiographs obtained annually from children recruited to the Canada-wide STeroid-Associated Osteoporosis in the Pediatric Population (STOPP) observational study, in which 400 children with glucocorticoid-treated leukemia, rheumatic disorders, and nephrotic syndrome were enrolled near glucocorticoid initiation and followed prospectively for 6 years. Normal variants mimicking fractures exist in all regions of the spine and fall into two groups. The first group comprises variants mimicking pathological vertebral height loss, including not-yet-ossified vertebral apophyses superiorly and inferiorly, which can lead to a vertebral shape easily over-interpreted as anterior wedge fracture, physiological beaking, or spondylolisthesis associated with shortened posterior vertebral height. The second group includes variants mimicking other radiologic signs of fractures: anterior vertebral artery groove resembling an anterior buckle fracture, Cupid's bow balloon disk morphology, Schmorl nodes mimicking concave endplate fractures, and parallax artifact resembling endplate interruption or biconcavity. If an unexpected vertebral body contour is detected, careful attention to its location, detailed morphology, and (if available) serial changes over time may clarify whether it is a fracture requiring change in management or simply a normal variant. Awareness of the variants described in this paper can improve accuracy in the diagnosis of pediatric vertebral fractures.

Observer agreement in pediatric semiquantitative vertebral fracture diagnosis.

BACKGROUND: The Genant semiquantitative (GSQ) method has been a standard procedure for diagnosis of vertebral fractures in adults but has only recently been shown to be of clinical utility in children. Observer agreement using the GSQ method in this age group has not been described. OBJECTIVE: To evaluate observer agreement on vertebral readability and vertebral fracture diagnosis using the GSQ method in pediatric vertebral morphometry. MATERIALS AND METHODS: Spine radiographs of 186 children with acute lymphoblastic leukemia were evaluated independently by three radiologists using the same GSQ methodology as in adults. A subset of 100 radiographs was evaluated on two occasions. RESULTS: An average of 4.7% of vertebrae were unreadable for the three radiologists. Intraobserver Cohen's kappa (κ) on readability ranged from 0.434 to 0.648 at the vertebral level and from 0.416 to 0.611 at the patient level, while interobserver κ for readability had a range of 0.330 to 0.504 at the vertebral level and 0.295 to 0.467 at the patient level. Intraobserver κ for the presence of vertebral fracture had a range of 0.529 to 0.726 at the vertebral level and was 0.528 to 0.767 at the patient level. Interobserver κ for fracture at the vertebral level ranged from 0.455 to 0.548 and from 0.433 to 0.486 at the patient level. CONCLUSION: Most κ values for both intra- and interobserver agreement in applying the GSQ method to pediatric spine radiographs were in the moderate to substantial range, comparable to the performance of the technique in adult studies. The GSQ method should be considered for use in pediatric research and clinical practice.

Risk Factors Associated with Incident Vertebral Fractures in Steroid-treated Males with Duchenne Muscular Dystrophy.

PURPOSE: Prevention of fractures is an unmet need in glucocorticoid (GC)-treated Duchenne muscular dystrophy. This study explored factors associated with incident vertebral fractures (VFs) to inform future fracture prevention efforts. METHODS: VFs were evaluated prospectively at study baseline and 12 months on lateral spine radiographs in participants aged 4 to 25 years with Duchenne muscular dystrophy. Clinical factors were analyzed for their association with the change in Spinal Deformity Index (sum of the Genant-defined VF grades from T4 to L4) between baseline and 12 months. RESULTS: Thirty-eight males were evaluated (mean ± SD age at baseline 11.0 ± 3.6 years; mean ± SD GC duration at baseline 4.1 ± 3.1 years; 74% ambulatory). Nine of 38 participants (24%) had 17 incident VFs, of which 3/17 VFs (18%) were moderate/severe. Participants with 12-month incident VF had lower mean ± SD baseline lumbar spine areal bone mineral density Z-scores (-2.9 ± 1.0 vs -1.9 ± 1.1; P = .049) and lower total body less head areal bone mineral density Z-scores (-3.1 ± 1.2 vs -1.6 ± 1.7; P = .036). Multivariable linear regression showed that at least 1 VF at baseline (P < .001), a higher number of antecedent non-VF (P < .001), and greater bone age delay at baseline (P = .027) were significant predictors of an increase in the Spinal Deformity Index from baseline to 12 months. CONCLUSION: The observation that ≥ 1 prevalent VF and/or non-VF were the strongest predictors of incident VFs at 12 months supports the need for prevention of first fractures in this high-risk setting. Bone age delay, a marker of GC exposure, may assist in the prioritization of patients in efforts to prevent first fractures.

Vertebral Body Reshaping after Fractures: An Important Index of Recovery in Glucocorticoid-Treated Children.

PURPOSE: In this 6-year study we identified factors associated with spontaneous vertebral body reshaping in glucocorticoid (GC)-treated children with leukemia, rheumatic disorders, and nephrotic syndrome. METHODS: Subjects were 79 children (mean age 7.4 years) who had vertebral fracture (VF) evaluation on lateral spine radiographs at least 1 year after VF detection. VF were graded using the modified Genant semiquantitative method and fracture burden for individuals was quantified using the spinal deformity index (SDI; sum of grades from T4 to L4). RESULTS: Sixty-five children (82.3%) underwent complete vertebral body reshaping (median time from VF detection to complete reshaping 1.3 years by Cox proportional hazard modeling). Of 237 VF, the majority (83.1%) ultimately reshaped, with 87.2% reshaping in the thoracic region vs 70.7% in the lumbar region (P = .004). Cox models showed that (1) every g/m2 increase in GC exposure in the first year after VF detection was associated with a 19% decline in the probability of reshaping; (2) each unit increase in the SDI at the time of VF detection was associated with a 19% decline in the probability of reshaping [hazard ratio (HR) = 0.81; 95% confidence interval (CI) = 0.71, 0.92; P = .001]; (3) each additional VF present at the time of VF detection reduced reshaping by 25% (HR = 0.75; 95% CI = 0.62, 0.90; P = .002); and (4) each higher grade of VF severity decreased reshaping by 65% (HR = 0.35; 95% CI = 0.21, 0.57; P < .001). CONCLUSION: After experiencing a VF, children with higher GC exposure, higher SDI, more severe fractures, or lumbar VF were at increased risk for persistent vertebral deformity.

Use of exclusive enteral nutrition is just as effective as corticosteroids in newly diagnosed pediatric Crohn's disease.

BACKGROUND: The efficacy of exclusive enteral nutrition (EEN) in induction of remission in pediatric Crohn's disease (CD) is reported to be equivalent to that of corticosteroids (CS). AIMS: Our objective was to compare the efficacy of EEN and CS in inducing remission in pediatric onset CD and the effects of the treatment on nutritional status and bone mineral density (BMD). METHODS: Medical charts were retrospectively studied for patients diagnosed with CD between 2000 and 2010 at the Stollery children's hospital in Edmonton, Alberta. Anthropometric and dual-energy X-ray absorptiometry (DXA) data were collected to assess effects of therapy; clinical remission, relapse, and severity were defined on the basis of the pediatric Crohn's disease activity index. RESULTS: To induce remission at first presentation, 36 patients (mean age 12.9 years) received EEN and 69 (mean age 11.2 years) received CS. Remission (88.9% in the EEN group versus 91.3% in the CS group (p=0.73) at 3 months) and relapse (40.6 vs. 28.6%, respectively (p=0.12) over 12 months) were similar in both treatment groups. Thirty-four patients had paired DXA scans at the time of diagnosis and one year later: 16 given EEN and 18 given CS. Change in BMD spine z-scores based on bone age adjusted for height and chronological age was greater for EEN patients but not statistically significant (Δz-score 0.30 vs. 0.03, p=0.28). CONCLUSIONS: EEN has similar efficacy to corticosteroids; however, EEN may lead to better BMD accrual. EEN should be preferred to corticosteroids as first-line therapy for induction of remission in pediatric CD.

A workstation-integrated peer review quality assurance program: pilot study.

BACKGROUND: The surrogate indicator of radiological excellence that has become accepted is consistency of assessments between radiologists, and the technique that has become the standard for evaluating concordance is peer review. This study describes the results of a workstation-integrated peer review program in a busy outpatient radiology practice. METHODS: Workstation-based peer review was performed using the software program Intelerad Peer Review. Cases for review were randomly chosen from those being actively reported. If an appropriate prior study was available, and if the reviewing radiologist and the original interpreting radiologist had not exceeded review targets, the case was scored using the modified RADPEER system. RESULTS: There were 2,241 cases randomly assigned for peer review. Of selected cases, 1,705 (76%) were interpreted. Reviewing radiologists agreed with prior reports in 99.1% of assessments. Positive feedback (score 0) was given in three cases (0.2%) and concordance (scores of 0 to 2) was assigned in 99.4%, similar to reported rates of 97.0% to 99.8%. Clinically significant discrepancies (scores of 3 or 4) were identified in 10 cases (0.6%). Eighty-eight percent of reviewed radiologists found the reviews worthwhile, 79% found scores appropriate, and 65% felt feedback was appropriate. Two-thirds of radiologists found case rounds discussing significant discrepancies to be valuable. CONCLUSIONS: The workstation-based computerized peer review process used in this pilot project was seamlessly incorporated into the normal workday and met most criteria for an ideal peer review system. Clinically significant discrepancies were identified in 0.6% of cases, similar to published outcomes using the RADPEER system. Reviewed radiologists felt the process was worthwhile.

Reductions in Bone Mineral Density Are Apparent Early in Children With Prevalent Osteonecrosis Lesions Following Leukemia Therapy.

Osteonecrosis (ON) is a serious complication of childhood acute lymphoblastic leukemia. We determined the prevalence of osteonecrotic lesions in our patient population by a one-time multisite magnetic resonance imaging (MRI) more than 1 year following leukemia therapy. MRI findings were evaluated in relationship to clinical factors (including longitudinal changes in bone mineral density [BMD]). Eighty-six children enrolled in the Steroid Associated Osteoporosis in the Pediatric Population (STOPP) study were evaluated for ON at 3.1 ± 1.3 years following therapy. Thirty children had a total of 150 confirmed ON lesions (35%). Lumbar spine (LS) BMD Z-scores (mean ± SD) were low at diagnosis and similar between patients with and without ON (-1.09 ± 1.53 versus -1.27 ± 1.25, p = 0.549). LS BMD Z-scores declined from baseline to 12 months in children with ON (-0.31 ± 1.02) but not in those without (0.13 ± 0.82, p = 0.035); the hip BMD Z-scores from baseline to 24 months declined in both groups, but to a greater extent in those with ON (-1.77 ± 1.22) compared to those without (-1.03 ± 1.07, p = 0.045). At the time of the MRI, mean total hip and total body (TB) BMD Z-scores were lower in children with ON (hip -0.98 ± 0.95 versus -0.28 ± 1.06, p = 0.010; TB -1.36 ± 1.10 versus -0.48 ± 1.50, p = 0.018). Pain occurred in 11/30 (37%) with ON versus 20/56 (36%) without, p = 0.841. In multivariable models, older age at diagnosis (odds ratio [OR] 1.57; 95% confidence interval [CI], 1.15-2.13; p = 0.004), and hip BMD Z-score at MRI (OR 2.23; 95% CI, 1.02-4.87; p = 0.046) were independently associated with ON. Overall, one-third of children demonstrated ON after leukemia therapy. Those with ON had greater reductions in spine and hip BMD Z-scores in the first 1 and 2 years of therapy, respectively. Older age and lower hip BMD Z-scores at MRI were significantly associated with prevalent, off-therapy ON. These data assist in identifying children at risk of ON. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The Accuracy of Incident Vertebral Fracture Detection in Children Using Targeted Case-Finding Approaches.

Vertebral fractures are clinically important sequelae of a wide array of pediatric diseases. In this study, we examined the accuracy of case-finding strategies for detecting incident vertebral fractures (IVF) over 2 years in glucocorticoid-treated children (n = 343) with leukemia, rheumatic disorders, or nephrotic syndrome. Two clinical situations were addressed: the prevalent vertebral fracture (PVF) scenario (when baseline PVF status was known), which assessed the utility of PVF and low lumbar spine bone mineral density (LS BMD; Z-score <-1.4), and the non-PVF scenario (when PVF status was unknown), which evaluated low LS BMD and back pain. LS BMD was measured by dual-energy X-ray absorptiometry, vertebral fractures were quantified on spine radiographs using the modified Genant semiquantitative method, and back pain was assessed by patient report. Forty-four patients (12.8%) had IVF. In the PVF scenario, both low LS BMD and PVF were significant predictors of IVF. Using PVF to determine which patients should have radiographs, 11% would undergo radiography (95% confidence interval [CI] 8-15) with 46% of IVF (95% CI 30-61) detected. Sensitivity would be higher with a strategy of PVF or low LS BMD at baseline (73%; 95% CI 57-85) but would require radiographs in 37% of children (95% CI 32-42). In the non-PVF scenario, the strategy of low LS BMD and back pain produced the highest specificity of any non-PVF model at 87% (95% CI 83-91), the greatest overall accuracy at 82% (95% CI 78-86), and the lowest radiography rate at 17% (95% CI 14-22). Low LS BMD or back pain in the non-PVF scenario produced the highest sensitivity at 82% (95% CI 67-92), but required radiographs in 65% (95% CI 60-70). These results provide guidance for targeting spine radiography in children at risk for IVF. © 2021 American Society for Bone and Mineral Research (ASBMR).

Osteoporotic Fractures and Vertebral Body Reshaping in Children With Glucocorticoid-treated Rheumatic Disorders.

CONTEXT: Osteoporotic fractures are an important cause of morbidity in children with glucocorticoid-treated rheumatic disorders. OBJECTIVE: This work aims to evaluate the incidence and predictors of osteoporotic fractures and potential for recovery over six years following glucocorticoid (GC) initiation in children with rheumatic disorders. METHODS: Children with GC-treated rheumatic disorders were evaluated through a prospective inception cohort study led by the Canadian STeroid-induced Osteoporosis in the Pediatric Population (STOPP) Consortium. Clinical outcomes included lumbar spine bone mineral density (LS BMD), vertebral fractures (VF), non-VF, and vertebral body reshaping. RESULTS: A total of 136 children with GC-treated rheumatic disorders were enrolled (mean age 9.9 years, SD 4.4). The 6-year cumulative fracture incidence was 16.3% for VF, and 10.1% for non-VF. GC exposure was highest in the first 6 months, and 24 of 38 VF (63%) occurred in the first 2 years. Following VF, 16 of 19 children (84%) had complete vertebral body reshaping. Increases in disease activity and body mass index z scores in the first year and declines in LS BMD z scores in the first 6 months predicted incident VF over the 6 years, while higher average daily GC doses predicted both incident VF and non-VF. LS BMD z scores were lowest at 6 months (mean -0.9, SD 1.2) and remained low by 6 years even when adjusted for height z scores (-0.6, SD 0.9). CONCLUSION: VF occurred early and were more common than non-VF in children with GC-treated rheumatic disorders. Eighty-four percent of children with VF underwent complete vertebral body reshaping, whereas vertebral deformity persisted in the remainder of children. On average, LS BMD z scores remained low at 6 years, consistent with incomplete recovery.

The Accuracy of Prevalent Vertebral Fracture Detection in Children Using Targeted Case-Finding Approaches.

Due to concerns about cumulative radiation exposure in the pediatric population, it is not standard practice to perform spine radiographs in most conditions that predispose to vertebral fracture (VF). In this study we examined the accuracy of two clinical predictors, back pain and lumbar spine bone mineral density (LS BMD), to derive four case-finding paradigms for detection of prevalent VF (PVF). Subjects were 400 children at risk for PVF (leukemia 186, rheumatic disorders 135, nephrotic syndrome 79). Back pain was assessed by patient report, LS BMD was measured by dual-energy X-ray absorptiometry, and PVF were quantified on spine radiographs using the modified Genant semiquantitative method. Forty-four patients (11.0%) had PVF. Logistic regression analysis between LS BMD and PVF produced an odds ratio (OR) of 1.9 (95% confidence interval [CI], 1.5 to 2.5) per reduction in Z-score unit, an area under the receiver operating characteristic curve of 0.70 (95% CI, 0.60 to 0.79), and an optimal BMD Z-score cutoff of -1.6. Case identification using either low BMD alone (Z-score < -1.6) or back pain alone gave similar results for sensitivity (55%, 52%, respectively), specificity (78%, 81%, respectively), positive predictive value (PPV; 24%, 25%, respectively), and negative predictive value (NPV; 93%, 93%, respectively). The paradigm using low BMD plus back pain produced lower sensitivity (32%), higher specificity (96%), higher PPV (47%), and similar NPV (92%). The approach using low BMD or back pain had the highest sensitivity (75%), lowest specificity (64%), lowest PPV (20%), and highest NPV (95%). All paradigms had increased sensitivities for higher fracture grades. Our results show that BMD and back pain history can be used to identify children with the highest risk of PVF so that radiography can be used judiciously. The specific paradigm to be applied will depend on the expected PVF rate and the clinical approach to the use of radiography. © 2019 American Society for Bone and Mineral Research.

Persistence of Sarcopenia After Pediatric Liver Transplantation Is Associated With Poorer Growth and Recurrent Hospital Admissions.

INTRODUCTION: Sarcopenia is prevalent in adults pre-liver transplantation (LTx) and post-LTx contributing to adverse outcomes. Little is known regarding the prevalence of sarcopenia in pediatric LTx recipients. This novel study examined sarcopenia prevalence and associations with post-LTx growth and healthcare utilization in pediatric LTx recipients. METHODS: We prospectively assessed body composition at annual clinical appointments in children (0.5-17 years; n = 58) by Dual-energy-X-ray absorptiometry (absolute/regional/percent fat mass [FM], fat-free mass [FFM], skeletal muscle mass [SMM]). Sarcopenia was defined as SMM z scores ≤2. Additional variables measured included age, gender, PELD, immunosuppressive therapies (dose/type), weight, weight-z, height, height-z, serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, albumin, total/conjugated bilirubin, prothrombin time, international normalized ratio, albumin, creatinine clearance, urea and creatinine at LTx assessment, LTx and annual clinic appointments. Healthcare variables studied included rejection (number/type/severity), length of in-patient stay (total, intensive care unit [ICU], emergency, readmission) and ventilator dependency. RESULTS: Sarcopenia occurred in 41% (n = 17) at 7.6 (± 3.1) years; with a mean time post-LTx of 1.1 ± 1.9 (1-8) years. Female children ≤9.8 years had a higher sarcopenia prevalence than children >9.8 years (83.1% vs 17.1%; p = 0.004). Sarcopenia was associated with lower weight velocity standard deviation scores, lower weight-z/height-z scores at 2-10 years post LTx, increased hospitalization (total, ICU, emergency and readmission) and ventilator dependency (p < 0.05), but not to rejection and/or corticosteroid therapy (p > 0.05). CONCLUSIONS: This is the first study demonstrating persistent sarcopenia associated with poorer growth and recurrent hospitalization in children post-LTx.

Impact of Vertebral Fractures and Glucocorticoid Exposure on Height Deficits in Children During Treatment of Leukemia.

Objective: To assess the effect of vertebral fractures (VF) and glucocorticoid (GC) exposure on height deficits in children during treatment of acute lymphoblastic leukemia (ALL). Methods: Children with ALL treated without cranial radiation therapy (n = 160; median age, 5.1 years; 58.1% male) were followed prospectively for 6 years. Spinal deformity index (SDI) was used to quantify VF status. Results: Baseline height z score ± SD was 0.3 ± 1.2. It fell by 0.5 ± 0.4 in the first 6 months for boys and by 0.4 ± 0.4 in the first 12 months for girls (P < 0.01 for both) and then subsequently recovered. The prevalence of VF peaked at 1 year (17.6%). Among those with VF, median SDI rose from 2 [interquartile range (IQR): 1, 7] at baseline to 8 (IQR: 1, 8) at 1 year. A mixed model for repeated measures showed that height z score declined by 0.13 (95% CI: 0.02 to 0.24; P = 0.02) for each 5-unit increase in SDI during the previous 12 months. Every 10 mg/m2 increase in average daily GC dose (prednisone equivalent) in the previous 12 months was associated with a height z score decrement of 0.26 (95% CI: 0.20 to 0.32; P < 0.01). Conclusions: GC likely plays a major role in the observed height decline during therapy for ALL. Because only a minority of children had VF, fractures could not have contributed significantly to the height deficit in the entire cohort but may have been important among the subset with VF.