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.

Cohort profile update: The Canadian Maternal-Infant Research on Environmental Chemicals Child Development study (MIREC-CD PLUS).

BACKGROUND: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women. OBJECTIVES: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood. POPULATION: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits. PRELIMINARY RESULTS: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). CONCLUSIONS: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development.

Very severe hypertriglyceridemia complicating pediatric acute lymphoblastic leukemia treatment: a call for management guidelines.

OBJECTIVES: Severe and very severe hypertriglyceridemia although rare within the pediatric population occur more often among oncology patients, secondary to chemotherapeutic agents. Currently there exists minimal literature to guide management of severe hypertriglyceridemia among pediatric patients. Very-low-fat dietary restriction should be considered over nil per os (NPO) for initial management of severe hypertriglyceridemia in stable pediatric patients. Pediatricians caring for oncology patients must consider chylomicronemia as a potential etiology for presenting symptoms. Pediatric severe hypertriglyceridemia management guidelines are needed as pediatricians must currently rely on anecdotal experiences for management decisions. CASE PRESENTATION: Three children receiving treatment for acute lymphoblastic leukemia required hospitalization for very severe hypertriglyceridemia. Management varied among the cases but included: NPO or very-low-fat diet, insulin, intravenous fluids, fibrates, and omega-3 fatty acids. CONCLUSIONS: These cases suggest that pediatric severe hypertriglyceridemia management, in the absence of pancreatitis should allow a very-low-fat diet initially rather than NPO followed by pharmacologic therapies.

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.

The Detection, Evaluation, and Management of Dyslipidemia in Children and Adolescents: A Canadian Cardiovascular Society/Canadian Pediatric Cardiology Association Clinical Practice Update.

Atherosclerosis begins in youth and is directly linked with the presence and severity of cardiovascular risk factors, including dyslipidemia. Thus, the timely identification and management of dyslipidemia in childhood might slow atherosclerotic progression and decrease the risk of cardiovascular disease in adulthood. This is particularly true for children with genetic disorders resulting in marked dyslipidemia, including familial hypercholesterolemia, which remains frequently undiagnosed. Universal and cascade screening strategies can effectively identify cases of pediatric dyslipidemia. In the clinical evaluation of children with dyslipidemia, evaluating for secondary causes of dyslipidemia, including medications and systemic disorders is essential. The first line therapy generally centres around lifestyle modifications, with dietary changes specific to the dyslipidemia phenotype. Indications for medication depend on the severity of dyslipidemia and an individualized assessment of cardiovascular risk. Despite an expanding evidence base supporting the detection and timely management of pediatric dyslipidemia, numerous knowledge gaps remain, including a sufficient evidence base to support more widespread screening, thresholds for initiation of pharmacotherapy, and treatment targets. Further studies on the most appropriate age for statin initiation and long-term safety studies of statin use in youth are also required. The most pressing matter, however, is the development of knowledge translation strategies to improve the screening and detection of lipid disorders in Canadian youth.

Dietary compliance in a randomized double-blind infant feeding trial during infancy aiming at prevention of type 1 diabetes.

The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) tested the hypothesis whether extensively hydrolyzed casein-based versus regular cow's milk-based infant formula reduces the risk of type 1 diabetes. We describe dietary compliance in the trial in terms of study formula intake, feeding of nonrecommended foods, and serum cow's milk antibody concentration reflecting intake of cow's milk protein among 2,159 eligible newborn infants with a biological first-degree relative affected by type 1 diabetes and with HLA-conferred susceptibility to type 1 diabetes. The participating infants were introduced to the study formula feeding at the median age of 15 days with a median duration of study formula use of 63 days. During the intervention, 80% of the infants received study formula. Of these, 57% received study formula for at least 2 months. On average, 45.5 l of study formula were used per infant. Only 13% of the population had received a nonrecommended food by the age of 6 months. The dietary compliance was similar in the intervention and control arm. The reported cow's milk consumption by the families matched very well with measured serum casein IgA and IgG antibody concentration. To conclude, good compliance was observed in this randomized infant feeding trial. Compliance varied between the regions and those infants who were breastfed for a longer period of time had a shorter exposure to the study formula. High dietary compliance in infant feeding trial is necessary to allow accurate interpretation of study results.

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.

Central diabetes insipidus and pain medications - a risky combination.

BACKGROUND: Central Diabetes Insipidus (CDI) results from decreased production of antidiuretic hormone (ADH) leading to an inability to concentrate urine. CDI is treated with desmopressin (DDAVP). Rarely reported in the literature, opioids and non-steroidal anti-inflammatories (NSAIDs) can induce hyponatremia in individuals treated for CDI. CASE PRESENTATION: A 10-year-old boy with septo-optic dysplasia and CDI was treated with DDAVP 1.6 mg orally TID maintaining normal sodium levels. Post admission for a femur fracture, he was discharged on ibuprofen and hydromorphone. Sodium was 136 mmol/l two days before discharge. He returned to the ED after having a seizure at home. He was euvolemic and mildly lethargic. Sodium was low at 108 mmol/l. DDAVP and hydromorphone were held and he was fluid restricted, but the sodium remained low. Sodium began to rise when Ibuprofen was stopped. Intermittent small doses of DDAVP were given to facilitate gradual correction of hyponatremia. At discharge, sodium had normalized. CONCLUSION: Hyponatremia has occasionally been described as a side effect of opioids and rarely of NSAIDs in patients with CDI. Stimulation of the thirst centre may play a role with opioids while a decrease in urine output may be the mechanism with NSAIDs.

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).

Experience of Caring for a Child With Type 1 Diabetes Mellitus in a Food-Insecure Household: A Qualitative Evaluation.

OBJECTIVES: An earlier study from Nova Scotia showed that food insecurity (FI) is more prevalent (21.9%) in families of children with diabetes, yet little is known about its impact on these families. We aimed to describe the day-to-day experiences of families living with FI while caring for a child with type 1 diabetes (T1D). METHODS: This investigation was a qualitative study with thematic analyses using semistructured interviews to explore perceptions of caregivers living with pediatric T1D and FI (N=13 households). RESULTS: Three major themes emerged: 1) FI had a disproportionate impact on families after T1D diagnosis compared with before diagnosis. The cost of healthy food threatened food security before T1D; however, there is increased hardship once high-quality food and hypoglycemia supplies are required. 2) Sacrifices to combat FI have disproportionate impacts among family members. At times, caregivers sacrificed the needs (food, medicine) of other family members (including children) to prioritize the needs of the child with T1D. 3) Caregivers perceived T1D needs as posing unique barriers to traditional FI supports, such as school breakfast programs. CONCLUSIONS: This study provides insight into the realities of life with pediatric T1D and FI. Living with T1D and FI poses challenges, and caregivers often cope by making difficult choices when providing for their family. Caregivers struggled to meet dietary recommendations while finding that T1D needs are often not met by traditional FI supports. This suggests that T1D clinicians should assess FI and help families in problem solving to mitigate its impact.

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.

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.

Bone Morbidity and Recovery in Children With Acute Lymphoblastic Leukemia: Results of a Six-Year Prospective Cohort Study.

Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL). Our objective was to determine the incidence and predictors of fractures and recovery from osteoporosis in pediatric ALL over 6 years following glucocorticoid initiation. Vertebral fractures (VF) and vertebral body reshaping were assessed on annual spine radiographs, low-trauma non-VF were recorded at regular intervals and spine bone mineral density (BMD) was captured every 6 months for 4 years and then annually. A total of 186 children with ALL were enrolled (median age 5.3 years; range, 1.3 to 17.0 years). The cumulative fracture incidence was 32.5% for VF and 23.0% for non-VF; 39.0% of children with VF were asymptomatic. No fractures occurred in the sixth year and 71.3% of incident fractures occurred in the first 2 years. Baseline VF, cumulative glucocorticoid dose, and baseline lumbar spine (LS) BMD Z-score predicted both VF and non-VF. Vertebral body reshaping following VF was incomplete or absent in 22.7% of children. Those with residual vertebral deformity following VF were older compared to those without (median age 8.0 years at baseline [interquartile range {IQR}, 5.5 to 9.4] versus 4.8 years [IQR, 3.6 to 6.2], p = 0.04) and had more severe vertebral collapse (median maximum spinal deformity index 3.5 [IQR, 1.0 to 8.0] versus 0.5 [IQR, 0.0 to 1.0], p = 0.01). VF and low LS BMD Z-score at baseline as well as glucocorticoid exposure predicted incident VF and non-VF. Nearly 25% of children had persistent vertebral deformity following VF, more frequent in older children, and in those with more severe collapse. These results suggest the need for trials addressing interventions in the first 2 years of chemotherapy, targeting older children and children with more severe vertebral collapse, because these children are at greatest risk for incident VF and subsequent residual vertebral deformity. © 2018 American Society for Bone and Mineral Research.

Disaster Preparedness among Health Professionals and Support Staff: What is Effective? An Integrative Literature Review.

Introduction It is important that health professionals and support staff are prepared for disasters to safeguard themselves and the community during disasters. There has been a significantly heightened focus on disasters since the terrorist attacks of September 11, 2001 in New York (USA); however, despite this, it is evident that health professionals and support staff may not be adequately prepared for disasters. Report An integrative literature review was performed based on a keyword search of the major health databases for primary research evaluating preparedness of health professionals and support staff. The literature was quality appraised using a mixed-methods appraisal tool (MMAT), and a thematic analysis was completed to identify current knowledge and gaps. Discussion The main themes identified were: health professionals and support staff may not be fully prepared for disasters; the most effective content and methods for disaster preparedness is unknown; and the willingness of health professionals and support staff to attend work and perform during disasters needs further evaluation. Gaps were identified to guide further research and the creation of new knowledge to best prepare for disasters. These included the need for: high-quality research to evaluate the best content and methods of disaster preparedness; inclusion of the multi-disciplinary health care team as participants; preparation for internal disasters; the development of validated competencies for preparedness; validated tools for measurement; and the importance of performance in actual disasters to evaluate preparation. CONCLUSION: The literature identified that all types of disaster preparedness activities lead to improvements in knowledge, skills, or attitude preparedness for disasters. Most studies focused on external disasters and the preparedness of medical, nursing, public health, or paramedic professionals. There needs to be a greater focus on the whole health care team, including allied health professionals and support staff, for both internal and external disasters. Evaluation during real disasters and the use of validated competencies and tools to deliver and evaluate disaster preparedness will enhance knowledge of best practice preparedness. However, of the 36 research articles included in this review, only five were rated at 100% using the MMAT. Due to methodological weakness of the research reviewed, the findings cannot be generalized, nor can the most effective method be determined. Gowing JR , Walker KN , Elmer SL , Cummings EA . Disaster preparedness among health professionals and support staff: what is effective? An integrative literature review. Prehosp Disaster Med. 2017;32(3):321-328.

Symptomatic adrenal suppression among children in Canada.

BACKGROUND: Adrenal suppression (AS) is an under-recognised side effect of glucocorticoid (GC) use. AS may go undetected until a physiological stress precipitates an adrenal crisis. The incidence of AS has not been established. We sought to estimate the minimum national incidence and presenting features of paediatric symptomatic AS. METHODS: Through the established methodology of the Canadian Paediatric Surveillance Program, over 2500 paediatricians were surveyed monthly for 2 years (April 2010-March 2012) to report new cases of symptomatic AS. RESULTS: Forty-six cases of symptomatic AS were confirmed. The estimated annual incidence is 0.35/100 000 children aged 0-18 years (95% CI 0.26 to 0.47). The most common presentations were growth failure (35%), non-specific symptoms (28%) or both (13%). Adrenal crisis occurred in six cases (13%). Thirty-seven children (80%) had received inhaled corticosteroid (ICS) alone or in combination with other GC forms. Many children received high but commonly prescribed doses of ICS. CONCLUSIONS: AS is responsible for significant morbidity in children, including susceptibility to adrenal crisis. The minimal estimated incidence reported is for the entire paediatric population and would be much higher in the at-risk group (ie, children treated with GCs). Close monitoring of growth and possible symptoms of AS, which may be non-specific, are important in children on all forms of GC therapy including ICS. To reduce the risk of AS, physicians must be aware of the risk of AS, revisit GC doses frequently and use the lowest effective dose.

Incident Vertebral Fractures in Children With Leukemia During the Four Years Following Diagnosis.

OBJECTIVES: The purpose of this article was to determine the incidence and predictors of vertebral fractures (VF) during the 4 years after diagnosis in pediatric acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Children were enrolled within 30 days of chemotherapy initiation, with incident VF assessed annually on lateral spine radiographs according to the Genant method. Extended Cox models were used to assess the association between incident VF and clinical predictors. RESULTS: A total of 186 children with ALL completed the baseline evaluation (median age, 5.3 years; interquartile range, 3.4-9.7 years; 58% boys). The VF incidence rate was 8.7 per 100 person-years, with a 4-year cumulative incidence of 26.4%. The highest annual incidence occurred at 12 months (16.1%; 95% confidence interval [CI], 11.2-22.7), falling to 2.9% at 4 years (95% CI, 1.1-7.3). Half of the children with incident VF had a moderate or severe VF, and 39% of those with incident VF were asymptomatic. Every 10 mg/m(2) increase in average daily glucocorticoid dose (prednisone equivalents) was associated with a 5.9-fold increased VF risk (95% CI, 3.0-11.8; P < .01). Other predictors of increased VF risk included VF at diagnosis, younger age, and lower spine bone mineral density Z-scores at baseline and each annual assessment. CONCLUSIONS: One quarter of children with ALL developed incident VF in the 4 years after diagnosis; most of the VF burden was in the first year. Over one third of children with incident VF were asymptomatic. Discrete clinical predictors of a VF were evident early in the patient's clinical course, including a VF at diagnosis.

Incident Vertebral Fractures and Risk Factors in the First Three Years Following Glucocorticoid Initiation Among Pediatric Patients With Rheumatic Disorders.

Vertebral fractures are an important yet underrecognized manifestation of osteoporosis in children with chronic, glucocorticoid-treated illnesses. Our goal was to determine the incidence and clinical predictors of vertebral fractures in the 3 years following glucocorticoid initiation among pediatric patients with rheumatic disorders. Incident vertebral fractures were evaluated according to the Genant semiquantitative method on lateral radiographs at baseline and then annually in the 3 years following glucocorticoid initiation. Extended Cox models were used to assess the association between vertebral fractures and clinical risk predictors. A total of 134 children with rheumatic disorders were enrolled in the study (mean ± standard deviation (SD) age 9.9 ± 4.4 years; 65% girls). The unadjusted vertebral fracture incidence rate was 4.4 per 100 person-years, with a 3-year incidence proportion of 12.4%. The highest annual incidence occurred in the first year (6.0%; 95% confidence interval (CI) 2.9% to 11.7%). Almost one-half of the patients with fractures were asymptomatic. Every 0.5 mg/kg increase in average daily glucocorticoid (prednisone equivalents) dose was associated with a twofold increased fracture risk (hazard ratio (HR) 2.0; 95% CI 1.1 to 3.5). Other predictors of increased vertebral fracture risk included: (1) increases in disease severity scores between baseline and 12 months; (2) increases in body mass index Z-scores in the first 6 months of each 12-month period preceding the annual fracture assessment; and (3) decreases in lumbar spine bone mineral density Z-scores in the first 6 months of glucocorticoid therapy. As such, we observed that a clinically significant number of children with rheumatic disorders developed incident vertebral fractures in the 3 years following glucocorticoid initiation. Almost one-half of the children were asymptomatic and thereby would have been undiagnosed in the absence of radiographic monitoring. In addition, discrete clinical predictors of incident vertebral fractures were evident early in the course of glucocorticoid therapy.