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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 Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

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., (© 2019 American Society for Bone and Mineral Research.)

Parity and lactation showed no associations with incident clinical fragility fractures or radiographic vertebral compression fractures in the 16-year CaMos prospective study. Parity was associated with slightly greater decline in femoral neck but not hip or spine areal bone mineral density (aBMD), while lactation showed no associations with aBMD change., Purpose: Pregnancy and especially lactation cause loss of bone mass and microarchitectural changes, which temporarily increase fracture risk. After weaning, aBMD increases but skeletal microarchitecture may be incompletely restored. Most retrospective clinical studies found neutral or even protective associations of parity and lactation with fragility fractures, but prospective data are sparse. CaMos is a randomly selected observational cohort that includes ~ 6500 women followed prospectively for over 16 years., Methods: We determined whether parity or lactation were related to incident clinical fragility fractures over 16 years, radiographic (morphometric and morphologic) vertebral fractures over 10 years, and aBMD change (spine, total hip, and femoral neck) over 10 years. Parity and lactation duration were analyzed as continuous variables in predicting these outcomes using univariate and multivariate regression analyses., Results: Three thousand four hundred thirty-seven women completed 16 years of follow-up for incident clinical fractures, 3839 completed 10 years of morphometric vertebral fracture assessment, 3788 completed 10 years of morphologic vertebral fracture assessment, and 4464 completed 10 years of follow-up for change in aBMD. In the multivariate analyses, parity and lactation duration showed no associations with clinical fragility fractures, radiographic vertebral fractures, or change in aBMD, except that parity associated with a probable chance finding of a slightly greater decline in femoral neck aBMD., Conclusions: Parity and lactation have no adverse associations with clinical fragility or radiographic vertebral fractures, or the rate of BMD decline over 10 years, in this prospective, multicenter study of a randomly selected, population-based cohort of women.

Until recently there has been little evidence available to validate any method by which to make an accurate diagnosis of an osteoporotic vertebral fractures (OVFs) from plain radiographs. In part this reflects a lack of a completely satisfactory "gold standard," but primarily it relates to the absence of well-designed prospective studies in this context. Historically, OVFs were recognized by evidence of macroscopic structural failure in vertebrae using the criteria applied elsewhere in the skeleton. This comprised altered alignment, fragmentation, cortical disruptions, and breaks, among other changes. However, these morphological criteria were replaced by vertebral morphometry, referring to the use of quantitative or quasi-quantitative measurement tools for fracture diagnosis. Vertebral morphometry emerged as an understanding of and treatment for osteoporosis evolved, mainly in response to the need for expeditious assessments of large numbers of spine images for epidemiological and pharmaceutical purposes. Although most of the descriptions of such morphometric tools have stressed that they were not to be applied to clinical diagnosis with respect to individual patients, this constraint has been widely disregarded. Here we review the major attempts to develop a diagnostic strategy for OVF and describe their characteristics in adults and children. Recent evidence suggests that morphometric (quantitative; ie, based on measurement of dimensions and shape description) criteria are inferior to morphologic (qualitative; ie, based on structural integrity) vertebral damage assessment in identifying people with low bone density and at an increased risk of future fracture. Thus there is now an evidentiary basis for suggesting that morphological assessment is the preferred strategy for use in diagnosing OVF from radiographs. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

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.

When a low-energy fracture occurs, then osteoporosis has progressed to the point of bony structural failure. Because vertebral fractures are the commonest type of osteoporotic fracture, the correct identification of them becomes important for diagnosis, risk estimation, and management. However, there are no uniformly agreed criteria for their diagnosis. The purpose of this review was to examine the diagnostic radiological strategies available and suggest a coherent approach to diagnosis. Diagnosis had come to focus on comparative changes in vertebral dimensions. However, it has become apparent that mild reductions in vertebral height are of uncertain implication. The importance of structural damage in diagnosis has become recognized in parallel. Relative reductions in vertebral height may not be a necessary nor sufficient criterion by which to diagnose a fracture., (Copyright © 2016 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Some 30 years ago the diagnosis of osteoporosis relied primarily on the measurement of bone mineral density by DXA. More recently, however, it was recognized that vertebral fractures are an important predictor of future fractures and that they reflect some aspect of bone fragility not captured by BMD measurement. In response to that, DXA manufacturers developed VFA, spine imaging on the densitometer, which allowed integration of BMD with information on vertebral fractures obtained at the same visit. ISCD has been instrumental in several aspects of VFA use such as developing and teaching courses for VFA or more broadly, for recognition of vertebral fractures; in developing guidelines for performance, interpretation and reporting of the VFA; and in advocating for reimbursement for VFA tests performed in the clinical practice. ISCD is poised to continue as a leader in vertebral fracture recognition and application of VFA to clinical practice and research., (Copyright © 2016 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2015 International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

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.

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., (© 2015 American Society for Bone and Mineral Research.)

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.

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.

The diagnosis of osteoporosis in men is controversial, although most studies demonstrate similar fracture rates for men and women with the same level of hip bone mineral density (BMD). Whether this applies to the lumbar spine is currently uncertain and has important implications with respect to choice of reference population for T-score calculation and osteoporosis diagnosis. This question was specifically addressed in the population-based Canadian Multicentre Osteoporosis Study cohort of 4745 women and 1887 men ages 50+ yr at the time of baseline lumbar spine dual energy x-ray absorptiometry. In up to 10 yr of observation, incident clinical major osteoporotic fractures occurred in 110 men (5.8%) vs 543 women (11.4%) (p < 0.001). Mean lumbar spine BMD in men was greater than in women, both among those with and those without incident major osteoporotic fracture (p < 0.001). Men were at slightly lower risk for incident major osteoporotic fracture than women for an equivalent lumbar spine BMD (age- and BMD-adjusted rate ratio 0.75, 95% confidence interval 0.60-0.93, p = 0.008) with similar findings after adjustment for the World Health Organization fracture risk assessment clinical risk factors or competing mortality. No significant sex difference in the BMD relationship was seen for vertebral fractures (clinical or radiographic) or for all fractures. In summary, this large population-based longitudinal cohort study found similar or lower fracture risk for men vs women after adjustment for absolute lumbar spine BMD and additional covariates. The least complicated model for describing fracture risk is therefore to use the same reference lumbar spine data for generating T-scores in men and women., (Copyright © 2014 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point., Introduction: Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome., Methods: VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry., Results: Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3-17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2-15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), -0.5 ± 1.1; p = 0.001) and at 3 months (-0.6 ± 1.1; p < 0.001), but not at 6 months (-0.3 ± 1.3; p = 0.066) or 12 months (-0.3 ± 1.2; p = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p = 0.003). A subgroup (N = 16; 25 %) had LS BMD Z-scores that were ≤-1.0 at 12 months. In these children, each additional 1,000 mg/m(2) of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, -0.71 to -0.07; p = 0.017)., Conclusions: The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤-1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.

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.

Summary: We compared the distribution of vertebral fractures in adults and children and found that fractures occurred in different locations in the two age groups. This likely relates to the different shape of the immature spine., Introduction: We hypothesized that the anatomical distribution of vertebral fractures (VF) would be different in children compared to adults., Methods: We compared the distribution of VF defined using the Genant semi-quantitative method (GSQ method) in adults (N = 221; 545 fractures) and in children early in the course of glucocorticoid therapy (N = 44; 94 fractures)., Results: The average age in the adult cohort was 62.9 years (standard deviation (SD), 13.4 years), 26% was male, the mean lumbar spine Z-score was -1.0 (SD, 1.5), and the corresponding T-score was -2.4 (SD, 1.4). The pediatric cohort median age was 7.7 years (range, 2.1-16.6 years), the mean lumbar spine Z-score was -1.7 (SD, 1.5), 52% was male, and disease categories were acute lymphoblastic leukemia (66%), rheumatological conditions (21%), and nephrotic syndrome (14%). The VF distribution was biphasic in both populations, but the peaks differed in location. In adults, the peaks were at T7/T8 and at T12/L1. In children, the focus was higher in the thoracic spine, at T6/T7, and lower in the lumbar spine, at L1/L2. When children were assessed in two age-defined sub-groups, a biphasic VF distribution was seen in both, but the upward shift of the thoracic focus to T6 was observed only in the older group, with the highest rates of fracture present between ages 7 and 10 years., Conclusions: These results suggest that the anatomical distribution of VF differs between children and adults, perhaps relating to the different shape of the immature spine, notably the changing ratio of kyphosis to lordosis.

Objective: 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., Methods: Children with rheumatic diseases initiating GC were enrolled in a prospective observational study. Annual spine radiographs were evaluated using the Genant semiquantitative method. Spine areal bone mineral density (aBMD) was measured every 6 months. Clinical features, including cumulative GC dose, back pain, disease and physical activity, calcium and vitamin D intake, and spine aBMD Z scores, were analyzed for association with IVF., Results: Seven (6%) of 118 children (95% confidence interval 2.9-11.7%) had IVF. Their diagnoses were: juvenile dermatomyositis (n = 2), systemic lupus erythematosus (n = 3), systemic vasculitis (n = 1), and mixed connective tissue disease (n = 1). One child was omitted from the analyses after 4 months because of osteoporosis treatment for symptomatic IVF. Children with IVF received on average 50% more GC than those without (P = 0.030), had a greater increase in body mass index (BMI) at 6 months (P = 0.010), and had greater decrements in spine aBMD Z scores in the first 6 months (P = 0.048). Four (67%) of 6 children with IVF and data to 12 months had spine aBMD Z scores less than -2.0 at 12 months compared to 16% of children without IVF (P = 0.011)., Conclusion: The incidence of VF 12 months following GC initiation was 6%; most children were asymptomatic. Children with IVF received more GC, had greater increases in BMI, and had greater declines in spine aBMD Z scores in the first 6 months., (Copyright © 2012 by the American College of Rheumatology.)

Objective: 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., Methods: Children were categorized as follows: juvenile dermatomyositis (n = 30), juvenile idiopathic arthritis (n = 28), systemic lupus erythematosus and related conditions (n = 26), systemic arthritis (n = 22), systemic vasculitis (n = 16), and other conditions (n = 12). Thoracolumbar spine radiograph and dual x-ray absorptiometry for lumbar spine (L-spine) areal bone mineral density (BMD) were performed within 30 days of glucocorticoid initiation. Genant semiquantitative grading was used for vertebral morphometry. Second metacarpal morphometry was carried out on a hand radiograph. Clinical factors including disease and physical activity, calcium and vitamin D intake, cumulative glucocorticoid dose, underlying diagnosis, L-spine BMD Z score, and back pain were analyzed for association with vertebral fracture., Results: Thirteen vertebral fractures were noted in 9 children (7%). Of these, 6 patients had a single vertebral fracture and 3 had 2-3 fractures. Fractures were clustered in the mid-thoracic region (69%). Three vertebral fractures (23%) were moderate (grade 2); the others were mild (grade 1). For the entire cohort, mean +/- SD L-spine BMD Z score was significantly different from zero (-0.55 +/- 1.2, P < 0.001) despite a mean height Z score that was similar to the healthy average (0.02 +/- 1.0, P = 0.825). Back pain was highly associated with increased odds for fracture (odds ratio 10.6 [95% confidence interval 2.1-53.8], P = 0.004)., Conclusion: In pediatric rheumatic conditions, vertebral fractures can be present prior to prolonged glucocorticoid exposure.

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.

Osteoporosis remains an important cause of morbidity and mortality especially in the elderly. This fact is largely due to fractures of the proximal femur and spine. As recently recognized, vertebral fractures are as much a threat to health and longevity as fractures of the proximal femur. In recent decades, the development of tools to evaluate fracture risk as well as medications to treat osteoporosis has altered the management of people who are at fracture risk. At the same time identification and management procedures concerning spinal fracturing are not very clear. Besides there is not even clear consensus about what exactly constitutes a vertebral fracture, particularly those of minor degree. While height loss is a simple and valuable tool to detect vertebral fractures, it is neither sensitive nor specific enough to replace radiographs. Some 65% of fractures cause no symptoms. Often vertebral fractures are misdiagnosed, especially if they have occurred silently and if the opportunity for diagnosis arises fortuitously. It is to the patient's benefit that radiologists report and physicians identify vertebral fractures evident on a chest or other radiograph, no matter how incidental to the immediate clinical indication for the examination. Technological evolution now allows dual-energy x-ray absorptiometry machines to be used to take spine images while doing a densitometry. The images are adequate, even if not of high radiographic quality, and, more important, the patient undergoes a smaller radiation dose than with conventional spinal radiographs. Such technology may promote fracture recognition. The recognition of vertebral fractures, as well as the prevention and treatment of further fractures, will likely do much to reduce both the burden of osteoporosis-related morbidity and mortality, as well as fracture-related costs to healthcare systems.