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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).

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.

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.

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.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 [abnormal3], lipid panel triglycerides, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol) and systolic/diastolic blood pressure (BP: absolute/z scores).Mean (±SD) age, weight z, height z, body mass index z was 9.7 ± 3.4 years (3.5-17.9), 0.26 ± 1.03, 0.017 ± 1.2, and 0.41 ± 1.05, 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 in5% 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.Pediatric LTx recipients with healthy body weights and corticosteroid-free immunosuppression have a low expression of CMD over 10 years.

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.

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.

Suboptimal vitamin D (vitD) status and reduced lean body mass are highly prevalent in pediatric inflammatory bowel diseases (IBD). The study objective was to determine sarcopenia prevalence and associations with vitD status in newly diagnosed pediatric IBD. Children with Crohn’s disease (CD; n = 58) and ulcerative colitis (UC; n = 27) were included. Primary outcomes included body composition (total/regional/percent fat mass (FM), fat-free mass (FFM), skeletal muscle mass (SMM)), and vitD status (serum 25(OH)D). Sarcopenia was defined as SMM-z

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.

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/m(2) 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.

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.

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.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.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 children9.8 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 (p0.05), but not to rejection and/or corticosteroid therapy (p0.05).This is the first study demonstrating persistent sarcopenia associated with poorer growth and recurrent hospitalization in children post-LTx.

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:Atotal 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/m2 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.

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.

Among women with obesity, those with the lowest bone density have the highest fracture risk. The types of fractures include any fracture, fragility-type fractures (vertebra, hip, upper arm, forearm, and lower leg), hand and foot fractures, osteoporotic, and other fracture types. Recent reports have contradicted the traditional view that obesity is protective against fracture. In this study, we have evaluated the relationship between fracture history and bone mineral density (BMD) in subjects with obesity. Fracture risk was assessed in 400 obese women in relation to body mass index (BMI), BMD, and clinical and laboratory variables. Subjects (mean age, 43.8 years; SD, 11.1 years) had a mean BMI of 46.0 kg/m2 (SD, 7.4 kg/m2). There were a total of 178 self-reported fractures in 87 individuals (21.8 % of subjects); fragility-type fractures (hip, vertebra, proximal humerus, distal forearm, and ankle/lower leg) were present in 58 (14.5 %). There were higher proportions of women in the lowest femoral neck BMD quintile who had any fracture history (41.3 vs. 17.2 %, p

Department of Radiology and Diagnostic Imaging and Division of Endocrinology and Metabolism, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada Department of Radiology, Le Centre hospitalier universitaire de Quebec, Quebec, Quebec, Canada Division of Endocrinology and Metabolism, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; representing the Canadian Panel of the International Society for Clinical Densitometry Division of Rheumatology, Department of Medicine, Laval University, Le Centre hospitalier universitaire de Quebec, Quebec, Quebec, Canada; representing the Scientific Advisory Council of Osteoporosis Canada

Patients with Crohn's disease have an increased frequency of osteopenia and osteoporosis. This randomized, controlled, double-blind study assessed the efficacy of risedronate versus placebo in treating low bone mineral density (BMD) in patients with Crohn's disease.88 Crohn's disease outpatients with BMD T-score-1.0 by dual-energy X-ray absorptiometry were randomly assigned to one of two treatment groups for the two year study duration: one group received risedronate 35 mg weekly while another received placebo. Both groups received daily calcium (Ca; 500 mg) and vitamin D (D; 400 IU) supplementation. Percent change in BMD relative to baseline was compared between the two therapies at 12 and 24 months.Using intent-to-treat analysis, at 12 months, risedronate+Ca+D increased BMD, relative to baseline, more than placebo+Ca+D in the femoral trochanter (1.4±3.4% vs -0.1±3.1%; p=0.03) and total hip (1.1±2.7% vs -0.1±2.5%;p=0.04). This trend in greater BMD continued for the 24 month duration of the study. There was no difference between the two treatment groups for changes in spine BMD. Subgroup analysis revealed that risedronate+Ca+D resulted in significantly better improvement in femoral trochanter BMD in non-smokers (p=0.01), males (p=0.01), those with a history of corticosteroid use in the preceding year (p=0.01), and current users of immunosuppressants (p=0.04).Risedronate, in addition to daily calcium and vitamin D supplementation, is superior to calcium and vitamin D alone in improving femoral trochanter and total hip BMD in patients with Crohn's disease.

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.

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.

Summary: Eighty children with nephrotic syndrome underwent lumbar spine densitometry and vertebral morphometry soon after glucocorticoid initiation. We found an inverse relationship between glucocorticoid exposure and spine areal bone mineral density (BMD) Z-score and a low rate of vertebral deformities (8%). Introduction: Vertebral fractures are an under-recognized complication of childhood glucocorticoid-treated illnesses. Our goal was to study the relationships among glucocorticoid exposure, lumbar spine areal BMD (LS BMD), and vertebral shape in glucocorticoid-treated children with new-onset nephrotic syndrome. Methods: Lateral thoracolumbar spine radiography and LS BMD were performed in 80 children with nephrotic syndrome (median age 4.4 years; 46 boys) within the first 37 days of glucocorticoid therapy. Genant semiquantitative grading was used as the primary method for vertebral morphometry; the algorithm-based qualitative (ABQ) method was used for secondary vertebral deformity analysis. Results: Six of the 78 children with usable radiographs (8%; 95% confidence interval 4 to 16%) manifested a single Genant grade 1 deformity each. All deformities were mild anterior wedging (two at each of T6, T7, and T8). Four of the 78 children (5%; 95% confidence interval 2 to 13%) showed one ABQ sign of fracture each (loss of endplate parallelism; two children at T6 and two at T8). Two of the children with ABQ signs also had a Genant grade 1 deformity in the same vertebral body. None of the children with a Genant or ABQ deformity reported back pain. An inverse relationship was identified between LS BMD Z-score and glucocorticoid exposure. Conclusions: Although we identified an inverse relationship between steroid exposure and LS BMD soon after glucocorticoid initiation for childhood nephrotic syndrome, there was only a low rate of vertebral deformities. The clinical significance of these findings requires further study. © 2011 International Osteoporosis Foundation and National Osteoporosis Foundation.

We identified hospitalizations throughout Canada during 2000–2005 in which the most responsible diagnosis was a proximal femoral fracture. Use of the US fracture risk assessment tool (FRAX) would be inappropriate for Canada as it would overestimate fracture risk in Canadian women and older men. It is recommended that the WHO fracture risk assessment tool should be calibrated to the target population. We identified hospitalizations for women and men throughout Canada during the study period 2000–2005 in which the most responsible diagnosis was a proximal femoral fracture (147,982 hip fractures). Age-standardized hip fracture rates were compared between Canadian provinces, and national rates were compared with those reported for the USA and Germany. There were relatively small differences in hip fracture rates between provinces, and most did not differ appreciably from the Canadian average. Hip fracture rates for women in Canada in 2001 were substantially lower than in the USA (population-weighted rate ratio 0.70) and were also lower than in Germany for 2004 (population-weighted rate ratio 0.74). Overall hip fracture rates for Canadian women were found to be substantially lower than those for the USA and Germany. This study underscores the importance of assessing country-specific fracture patterns prior to adopting an existing FRAX tool.

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 bone mineral density (BMD) and other clinical indices, have not been systematically studied. We evaluated spine health in 186 newly diagnosed children (median age 5.3 years, 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 semi-quantitative 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 bi-modal, with most occurring in the mid-thoracic and thoraco-lumbar regions. Children with grade 1 or higher vertebral compression had reduced lumbar spine (LS) areal BMD Z-scores compared to those without (mean±SD, −2.1±1.5 vs. −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% to 193%); the presence of back pain had an odds ratio of 4.7 (95% CI, 1.5 to 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.

Background & Aims: Vertebral fractures in Crohn's (CD) patients with low bone mineral density (BMD) have been documented as between 14%–22%. Vertebral fractures in CD patients with normal BMD have not been reported. The objectives were to identify the prevalence of vertebral fractures in CD patients and associated predictive factors. Methods: Two hundred twenty-four CD patients underwent vertebral BMD analysis and radiographs. Fractures were identified by using quantitative height reduction morphometry, and severity was assessed by spinal fracture index. Results: Mean age was 40.6 ± 11.0 years. Sixty percent reported corticosteroid use during the preceding year. Forty-five of 224 (20.0%) patients had 88 vertebral fractures. Sixteen of 45 patients with vertebral fractures had normal BMD (19.0% of all patients with normal BMD). Analysis of patients with or without vertebral fractures did not demonstrate significant differences in BMD or in corticosteroid use. Linear regression analysis demonstrated that elevations in body mass index, C-reactive protein, and parathyroid hormone were significantly predictive of vertebral fractures ( r = 0.415, P 20% ( r = 0.417, P Conclusions: This study demonstrates that vertebral fractures in CD patients occur with an equal frequency in those with low and with normal BMD, regardless of corticosteroid use. The mean age of CD patients with vertebral fractures was much lower than that reported in the general population for these fractures. Elevations in body mass index and C-reactive protein and parathyroid hormone levels were predictive of vertebral fractures.

It is important to understand how the move to absolute fracture risk estimation will affect patient categorization. We retrospectively compared categorization systems in 17,053 women aged 50 yr and older from a large referral database of clinical bone mineral density (BMD) tests. Densitometric systems (femoral neck alone or minimum value from spine, total hip, femoral neck, and trochanter) were taken to indicate high risk based upon T-score -2.5 or lower. Ten-year absolute fracture risk of the hip, spine, wrist, and proximal humerus was estimated from T-score and age, and a value greater than 20% was taken to indicate high risk. Using the femoral neck only, the densitometric system assigned 16.4% (95% confidence interval [CI]: 15.8-17.0%) of the entire study population to the high-risk category, whereas the 10-yr absolute fracture risk system using age and femoral neck T-score classified 20.3% (95% CI: 19.7-20.9, p0.0001) as high risk. When minimum T-score was used, the rates of high risk were similar using both approaches (31.4% [95% CI: 30.7-32.1] with the densitometric system vs 30.9% [95% CI: 30.2-31.6] for the 10-yr fracture risk system, p0.2). A 10-yr absolute fracture risk cutoff of 20% produced the best overall agreement with the densitometric systems. Below age 65 yr, the 10-yr fracture risk system resulted in a lower rate of high-risk categorization than the densitometric system. The profile reversed after age 65 yr, with a greater proportion considered high risk in the 10-yr fracture risk system compared to the densitometric system.

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.

The impact of clinical risk factor–based absolute risk methods on the prevalence of high risk for osteoporotic fracture is unknown. We applied absolute risk methods to 6646 subjects and found that the prevalence of elderly women deemed to be at high risk increased substantially, whereas the overall prevalence was highly dependent on the threshold used to designate high risk. Introduction: Many groups have advocated using absolute risk methods that incorporate clinical risk factors to target patients for osteoporosis therapy. We examined how the application of such absolute risk classification systems influences the prevalence of those considered to be at high risk for osteoporotic fracture and compared these systems to one based solely on BMD. Materials and Methods: Using 6646 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, randomly selected, population-based cohort, we assessed three different systems for determining prevalence of high risk for osteoporotic fracture: a BMD-based system; a simplified risk factor system incorporating age, sex, BMD, and two clinical risk factors; and a comprehensive system, incorporating age, sex, BMD, and seven clinical risk factors. The 10-year absolute risks of incident fragility fracture were compared across systems using three different high-risk thresholds. Results: The prevalence of a T score ≤ −2.5 was 18.8% (95% CI: 17.7–19.9%) in women and 3.9% (95% CI: 3.0–4.7%) in men. Using a 15% 10-year risk of fracture threshold, the prevalence of women at high risk increased to 46.9% (95% CI: 45.4–48.4) and 42.5% (95% CI: 41.1–43.9) when the comprehensive and simplified risk factor classification systems were used, respectively. Using a 25% 10-year absolute risk threshold, the prevalence of high risk was similar to that of the BMD-based system, whereas the 20% threshold gave intermediate rates. All thresholds analyzed resulted in an increased prevalence of older women at high risk for fracture, whereas only the 15% 10-year risk of fracture threshold resulted in an increase in the prevalence of men at high risk. Conclusions: The application of risk factor–based systems results in an increased prevalence of older women at high risk. The prevalence of individuals at high risk may increase with changes to the methods used to determine those who are eligible for therapy. These data have important implications for the pattern of care and costs of treating osteoporotic fractures.

Objective: To summarize the current knowledge regarding the impact of the most common antifracture medications on the various determinants of bone strength. Methods: Relevant English-language articles acquired from Medline from 1966 to January 2005 were reviewed. Searches included the keywords bone AND 1 of the following: strength, remodeling, microcrack, structure, mineralization, collagen, organic, crystallinity, osteocyte, porosity, diameter, anisotropy, stress risers, or connectivity AND alendronate, estrogen, etidronate, hormone replacement therapy, parathyroid hormone, risedronate, OR teriparatide. Abstracts from relevant conference proceedings were also reviewed for pertinent information. Results: Antiresorptive therapies increase bone strength through decreasing bone turnover. This lower bone turnover results in a higher mean mineralization and decreases the number of active resorption pits within bone at any given time. These resorption pits are speculated to be areas of focal weakness and a higher number of them would, if all other things were equal, result in greater fragility. Parathyroid hormone therapy increases the rate of bone remodeling, which introduces many resorption pits, but this source of strength loss is thought to be compensated by rapid increases in bone mass. Conclusions: Both the antiresorptives, particularly bisphosphonates, and the parathyroid hormone therapy increase bone strength; however, the changes that are elicited to achieve this differ significantly.

Background & Aims: Crohn's disease causes an increase in osteopenia and osteoporosis. This study assessed the efficacy of adding etidronate to calcium and vitamin D supplementation for treatment of low bone mineral density in Crohn's disease. Methods: One hundred fifty-four patients with Crohn's disease with decreased bone mineral density, determined by using dual-energy x-ray absorptiometry, were randomly assigned to receive etidronate (400 mg orally) or not for 14 days; both groups were then given daily calcium (500 mg) and vitamin D (400 IU) supplementation for 76 days. This cycle was repeated 8 times during a period of 24 months. Biochemical characteristics and bone mineral densities were assessed at 6, 12, and 24 months. Results: After 24 months bone mineral density significantly increased from baseline in both the etidronate- and the non-etidronate-treated groups (both groups receiving calcium and vitamin D supplementation) at the lumbar spine (P

A history of fracture and a low bone mineral density (BMD) are the strongest predictors of future osteoporotic fracture. This prospective cohort study assessed the impact of these two factors on treatment patterns in women undergoing their first BMD testing in a non-academic community setting. Successive women seen for first BMD testing at two testing centers completed a baseline questionnaire and a mailed 3-month follow-up questionnaire. Patients were grouped by history of fracture after age 20 years (present, absent) and by BMD result [osteoporosis (OP), osteopenia (OPN), normal BMD]. Thirty percent of 1144 patients at least 45 years old reported a history of fracture after age 20 years. They were no more likely than those without a history of fracture to be taking calcium (52% of total), vitamin D (31%), estrogen (31%), or a bisphosphonate (2%) before BMD testing. The BMD testing revealed OP in 20%, OPN in 45%, and normal BMD in 35%. Three months later, the percentages of patients taking treatments differed as follows: calcium (66 vs 53% in OP and OPN groups vs normal BMD), vitamin D (46 vs 37% in OPN group vs normal BMD), estrogen (25 vs 36 vs 44% in groups with OP, OPN, and normal BMD), a bisphosphonate (43 vs 11 vs 1%), and at least one of estrogen or a bisphosphonate (58 vs 43 vs 46%). Treatment decisions were influenced by first BMD testing but not significantly by a history of fracture. There is a substantial care gap in the treatment of patients with OP: either bisphosphonate or estrogen therapy was taken by only 31% of patients at least 45 years old and with a history of fracture after age 20 years before BMD testing and by only 58% of these and who also had OP by BMD.

Utilizing data from the Canadian Multicentre Osteoporosis Study (CaMos), we examined the association between potential risk factors and incident vertebral and nonvertebral fractures. A total of 5,143 postmenopausal women were enrolled. Information collected during the study included data from the CaMos baseline and annually mailed fracture questionnaires, the Short Form 36 (SF-36), the Health Utilities Index, and physical measurements. Participants were followed for 3 years. Postmenopausal women were classified into four groups according to their incident fracture status since baseline: those without a new fracture; those with a new clinically recognized vertebral fracture; those with an incident nonvertebral fracture at the wrist, hip, humerus, pelvis, or ribs (main nonvertebral fracture group); and those with any new nonvertebral fracture (any-nonvertebral-fracture group). We performed multivariate Cox proportional hazard analysis using all possible risk factors to determine the association between risk factors and the time to the first minimal trauma fracture. Best predictive models were also determined using variables that were included in the full models. The Bayesian information criterion was used for model selection. For all analyses, relative risks and associated 95% confidence intervals were calculated. During the follow-up period, 34, 163, and 280 women developed a vertebral, a main nonvertebral, or any nonvertebral fracture, respectively. The best predictive models indicated that a five point lower quality of life as measured by the SF-36 physical component summary score was associated with relative risks of 1.21 (95% CI, 1.02 to 1.44), 1.17 (95% CI, 1.07 to 1.28), and 1.19 (95% CI, 1.11 to 1.27) for incident vertebral, main nonvertebral, and all nonvertebral fractures, respectively. In addition, for a one standard deviation (SD=0.12) lower femoral neck BMD, the relative risks for incident vertebral, main nonvertebral, and any nonvertebral fractures increased by 2.73 (95% CI, 1.74 to 4.28), 1.39 (95% CI, 1.06 to 1.82), and 1.34 (95% CI, 1.09 to 1.65), respectively. Furthermore, various anthropometric measures, disease conditions, and medications are associated with a new fracture. Identifying postmenopausal women at risk is important given that fracture prevention therapies are now available.

Background: The SF-36 is widely used to assess health-related quality of life (HRQOL), but with few longitudinal studies in healthy populations, it is difficult to quantify its natural history. This is important because any measure of change following an intervention may be confounded by natural changes in HRQOL. This paper assesses mean changes in SF-36 scores over a 3-year period in men and women between the ages of 40 and 59 years at baseline. Methods: Subjects were randomly selected from nine Canadian cities. Mean SF-36 changes over a 3-year period (1996/1997-1999/2000) were calculated for each gender within 5-year age categories. Multiple imputation was used to correct for potential bias due to missing data. Results: The baseline cohort included 1,974 women and 975 men between 40 and 59 years. Mean changes in HRQOL tended to be small. Women demonstrated small average declines in 22 of the 32 age and domain groupings (4 age groups, 8 SF-36 domains) while men showed declines in 14/32. Most participants stayed within 10 points of their original baseline score. Interpretation: Mean SF-36 scores change only slightly over three years in middle-aged Canadians, although there is much individual variation. It may be necessary to adjust for the natural evolution of SF-36 scores when interpreting results from longitudinal studies.

Previous studies have confirmed that the prevalence of decreased bone mineral density is elevated in patients with inflammatory bowel disease. The objective of the current study was to determine the prevalence of osteopenia and osteoporosis in a cross-sectional outpatient population of 242 adult patients with Crohn's disease and to determine which clinical characteristics and serum and urine biochemical factors might be predictive of bone loss. Thirty-seven percent had normal bone density, 50.0% were osteopenic, and 12.9% were osteoporotic. Among the sites used to diagnose low bone mineral density, the femoral neck demonstrated the highest prevalence of osteopenia and the ultra-distal radius the highest prevalence of osteoporosis. However, low bone mineral density at one site was always predictive of low bone mineral density at the other. Corticosteroid use during the year before assessment was found to be consistently predictive of low bone mineral density in males but not in females. In contrast, low body mass index and high platelet counts were consistently predictive of low bone mineral density in females but not in males. Disease location, smoking, and age were not predictive of changes in bone mineral density.

Osteoporosis is underdiagnosed and therefore undertreated. We determined the potential usefulness of chest radiography for detecting clinically important vertebral fractures by performing semiquantitative reviews and quantitative digital morphometry on 100 routine chest radiographs taken in the emergency department and comparing the yield of these independent reviews with official radiology reports.One hundred randomly selected chest radiographs of patients 60 years or older who presented to the emergency department of a tertiary care hospital were evaluated. Radiographs were selected without knowledge of the presenting complaint and were independently reviewed by two board-certified radiologists and a radiology resident. A validated semiquantitative method was used to assess lateral chest radiographs for vertebral fracture. In addition, quantitative digital morphometry was undertaken. A clinically important vertebral fracture was defined as one that was at least moderate to severe (loss of heightor=25%).Mean age of the population was 75 years, 47% were women, and 46% were admitted to the hospital. According to the reference radiologist, prevalence of moderate to severe vertebral fractures was 22%. Simple agreement was 87-88% among reviewers; kappa values were moderate (0.56-0.58). The greatest agreement was between the reference standard radiologist and quantitative digital morphometry (89% agreement; kappa = 0.67). Only 55% (12/22) of vertebral fractures we identified were mentioned in the official radiology reports.Chest radiography has potential as a screening tool for revealing previously undiagnosed vertebral fractures, although in this study only half of moderate to severe fractures that we identified were mentioned in official reports.

OBJECTIVE: To evaluate the continued efficacy and safety of alendronate (ALN) for up to 2 years in patients receiving glucocorticoids. METHODS: This is a 12-month extension of a previously completed 1-year trial of daily ALN, performed to evaluate the effects of ALN over a total of 2 years in 66 men and 142 women continuing to receive at least 7.5 mg of prednisone or equivalent daily. All patients received supplemental calcium and vitamin D. The primary end point was the mean percentage change in lumbar spine bone mineral density (BMD) from baseline to 24 months. Other outcomes included changes in hip and total body BMD, biochemical markers of bone turnover, radiographic joint damage of the hands, and vertebral fracture incidence. RESULTS: The mean (+/-SEM) lumbar spine BMD increased by 2.8 +/- 0.6%, 3.9 +/- 0.7%, and 3.7 +/- 0.6%, respectively, in the groups that received 5 mg, 10 mg, and 2.5/10 mg of ALN daily (P < or = 0.001) and decreased by -0.8 +/- 0.6% in the placebo group (P not significant) over 24 months. In patients receiving any dose of ALN, BMD was increased at the trochanter (P < or = 0.05) and maintained at the femoral neck. Total body BMD was increased in patients receiving 5 or 10 mg ALN (P < or = 0.01). These 2 dose levels of ALN were more effective than placebo at all sites (P < or = 0.05). Bone turnover markers (N-telopeptides of type I collagen and bone-specific alkaline phosphatase) decreased 60% and 25%, respectively, during treatment with ALN (P < or = 0.05). There were fewer patients with new vertebral fractures in the ALN group versus the placebo group (0.7% versus 6.8%; P = 0.026). The safety profile was similar between treatment groups. CONCLUSION: Alendronate is an effective, well-tolerated therapy for the prevention and treatment of glucocorticoid-induced osteoporosis, with sustained treatment advantages for up to 2 years.

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. To evaluate observer agreement on vertebral readability and vertebral fracture diagnosis using the GSQ method in pediatric vertebral morphometry. 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. 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. 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.

Objectives: To educate scientists and health care providers about the effects ofcorticosteroids on bone, and advise clinicians of the appropriate treatments for patients receiving corticosteroids. Methods: This review summarizes the pathophysiology of corticosteroid-inducedosteoporosis, describes the assessment methods used to evaluate this condition, examines the results of clinical trials of drugs, and explores a practical approach to the management of corticosteroid-induced osteoporosis based on data collected from published articles. Results: Despite our lack of understanding about the biological mechanisms leading to corticosteroid-induced bone loss, effective therapy has been developed. Bisphosphonate therapy is beneficial in both the prevention and treatment of corticosteroid-induced osteoporosis. The data for the bisphosphonates are more compelling than for any other agent. For patients who have been treated but continue to lose bone, hormone replacement therapy, calcitonin, fluoride, or anabolic hormones should be considered. Calcium should be used only as an adjunctive therapy in the treatment or prevention of corticosteroid-induced bone loss and should be administered in combination with other agents. Conclusions: Bisophosphonates have shown significant treatment benefit and are the agents of choice for both the treatment and prevention corticosteroid-induced osteoporosis.

Patients admitted to the Phoenix Program for sex offender treatment at Alberta Hospital Edmonton were separated by family history into a group of North American Indians and a group of Caucasians, with respective sample sizes of 53 and 192 after range matching the Caucasian to the North American Indian sample on a number of demographic variables. Controlling for body mass index and age, the two groups were equivalent in terms of 12 basic blood chemistry variables and 5 of 6 endocrine measures. Serum testosterone did differ significantly (p < .0005, covariate adjusted means of 22.3 and 26.5 nmol/L, respectively, for Caucasians and North American Indians). Further research will be required to establish the generality of this result and to ascertain the etiology. © 1997 John Wiley & Sons, Inc. J Clin Psychol 53: 375–385, 1997.

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). 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). 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. 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). 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.

Age-standardized rates of hip fracture in Canada declined during the period 1985 to 2005. We investigated whether this incidence pattern is explained by period effects, cohort effects, or both. All hospitalizations during the study period with primary diagnosis of hip fracture were identified. Age- and sex-specific hip fracture rates were calculated for nineteen 5-year age groups and four 5-year calendar periods, resulting in 20 birth cohorts. The effect of age, calendar period, and birth cohort on hip fracture rates was assessed using age-period-cohort models as proposed by Clayton and Schiffers. From 1985 to 2005, a total of 570,872 hospitalizations for hip fracture were identified. Age-standardized rates for hip fracture have progressively declined for females and males. The annual linear decrease in rates per 5-year period were 12% for females and 7% for males (both p < 0.0001). Significant birth cohort effects were also observed for both sexes (p < 0.0001). Cohorts born before 1950 had a higher risk of hip fracture, whereas those born after 1954 had a lower risk. After adjusting for age and constant annual linear change (drift term common to both period and cohort effects), we observed a significant nonlinear birth cohort effect for males (p = 0.0126) but not for females (p = 0.9960). In contrast, the nonlinear period effect, after adjustment for age and drift term, was significant for females (p = 0.0373) but not for males (p = 0.2515). For males, we observed no additional nonlinear period effect after adjusting for age and birth cohort, whereas for females, we observed no additional nonlinear birth cohort effect after adjusting for age and period. Although hip fracture rates decreased in both sexes, different factors may explain these changes. In addition to the constant annual linear decrease, nonlinear birth cohort effects were identified for males, and calendar period effects were identified for females as possible explanations.

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. © 2012, American College of Rheumatology.

The clinical examination of neck masses is clearly imperfect and false-positive detection of thyroid nodules, termed "pseudonodules," remains a common problem. Movement on swallowing has been emphasized as a highly specific feature of thyroid masses, but lesions in the vicinity of the thyroid can be displaced by underlying structures during deglutition, causing them to mimic thyroid nodules. Two cases are presented to illustrate how additional features of neck mass movement can help determine whether a lesion is located within the thyroid or whether it is extrathyroidal. These include the range of motion of the mass, the presence or absence of a stationary phase prior to descent, and the timing of the movements of the mass. Assessment of these parameters during the physical examination of anterior neck masses may help reduce the incidence of thyroid pseudonodules.