Serum IGFBP-2 levels are associated with reduced insulin sensitivity in obese children.

Insulin-like growth factor binding protein 2 (IGFBP-2) may represent a critical link between body composition and insulin sensitivity. We investigated the relationship between circulating IGFBP-2 levels, body composition, insulin sensitivity, energy intake and physical activity in children with obesity. Children were recruited via the Weight Management Service at the Royal Children's Hospital, Melbourne, as part of the Childhood Overweight BioRepository of Australia (COBRA). Comprehensive anthropometric, biochemical and environmental data were collected and compared to serum IGFBP-2 levels (measured by enzyme-linked immunosorbent assay). Multiple regression modelling was used to assess the influence of circulating IGFBP-2 levels on anthropometric and biochemical measures. One hundred and ninety-four children were included in this study (46% male). Circulating IGFBP-2 negatively correlated with age, anthropometric measures, blood pressure and insulin concentration. Positive associations were observed between insulin sensitivity index-homeostasis model assessment (ISI-HOMA) and serum IGFBP-2. In multiple regression modelling, IGFBP-2 significantly contributes to variance in systolic blood pressure (-19%, P < 0.05), circulating triglycerides (-16%, P < 0.05) and ISI-HOMA (18%, P < 0.05). No associations were observed between dietary energy intake or physical activity and IGFBP-2 levels. Circulating IGFBP-2 levels in children with obesity correlate inversely with body mass and markers of metabolic dysfunction, and positively with insulin sensitivity. These findings suggest that reduced levels of IGFBP-2 may play an important role in the pathogenesis of obesity complications in early life.

What does a diagnostic label of 'polycystic ovary syndrome' really mean in adolescence? A review of current practice recommendations.

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, with many women initially presenting during adolescence. Diagnosis during this period is particularly challenging, yet many emphasize the importance of an early diagnosis given the long-term metabolic and reproductive health consequences associated with the syndrome. The objective of this study was to review the current literature to determine whether the diagnostic label 'PCOS' is necessary to effectively manage adolescent girls presenting with features of the syndrome. A literature search was conducted (PubMed, Medline, Informit Health and the Cochrane Database of Systematic Reviews) identifying papers addressing the diagnosis and management of PCOS during adolescence. Articles were selected based on date of publication, relevance of material and the quality of evidence presented. A total of 427 papers were screened, with 40 of these selected from the initial search. A subsequent 154 were included from manual review of reference lists from key papers identified in the initial search. Current guidelines recommend treating the individual manifestations of PCOS. In doing so, there is good evidence identifying that this approach adequately targets the underlying metabolic and reproductive changes associated with the syndrome. This suggests that providing a diagnostic label of PCOS is not actually necessary to effectively manage adolescent girls with features of this syndrome.

Longitudinal investigation of adenovirus 36 seropositivity and human obesity: the Cardiovascular Risk in Young Finns Study.

BACKGROUND/OBJECTIVES: Adenovirus-36 (Adv-36) infection is associated with exaggerated adipogenesis in cell culture and the development of obesity in animal models and humans, but a causal relationship remains unproven. Our objective was to determine whether serological evidence of Adv-36 infection in childhood and/or adulthood is associated with adult obesity. SUBJECTS/METHODS: Paired plasma concentrations of Adv-36 antibodies were measured by a novel enzyme-linked immunosorbent assay in a subgroup (n=449) of the Cardiovascular Risk in Young Finns Study in childhood (mean age 11.9 years) and adulthood (mean age 41.3 years). The study group included (1) individuals who had maintained normal-weight status (2) those who became obese adults from a normal-weight status in childhood and (3) those that were overweight/obese as a child and obese as an adult. RESULTS: Mean (s.d.) time between baseline and follow-up was 29.4 (3.2) years (range 21-31 years). A total of 24.4% of individuals who were normal weight throughout life were seropositive for Adv-36 during child and/or adulthood as compared with 32.3% of those who became obese adults (P=0.11). Those who became obese in adulthood were more likely to be Adv-36 seropositive as adults compared with those who maintained normal weight (21.3% vs. 11.6%, P=0.02). This difference was mediated by a decline in Adv-36 seropositivity between child and adulthood in those maintaining normal weight. No differences were observed in body mass index across the life course, nor in waist circumference in adult life, between those who were Adv-36 seronegative or seropositive at any age. CONCLUSIONS: Individuals who gained weight across the life course were more likely to be Adv-36 seropositive in adult life than those who did not gain weight. However, analysis of change in weight status in relation to Adv-36 positivity did not support a causal role for Adv-36 in the development of obesity.

The effect of antidepressants and antipsychotics on weight gain in children and adolescents.

Psychiatric illness in the paediatric population is increasing and the weight effect of medications for these problems is often unclear. A comprehensive literature search was undertaken to identify studies reporting weight in relation to antipsychotic and antidepressant use in children and adolescents. From 636 articles, 42 were selected for review. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) do not cause weight gain and may lead to improvements in weight status over the short, but not, long term. Antipsychotics were generally associated with weight gain. In drug comparison studies, risperidone had a larger weight gain effect than lithium, divalproex sodium and pimozide. Studies assessing the weight-protective effects of augmentation therapy with metformin or topiramate show less weight gain with addition of these agents. In conclusion, prescribing of SSRIs and SNRIs may be associated with improvements in weight status in children and adolescents but trials assessing their use in obesity, outside of established psychiatric illness, are limited and still experimental. Youth prescribed antipsychotic medication should be monitored for exaggerated weight gain and in those where obesity is a pre-existing concern agents other than olanzapine, clozapine and risperidone may be advantageous.

IGFBP-2 inhibits adipogenesis and lipogenesis in human visceral, but not subcutaneous, adipocytes.

BACKGROUND/OBJECTIVE: IGF-binding protein (IGFBP)-2 is the principal IGFBP produced by white adipocytes during adipogenesis, and circulating levels are reduced in obesity. Overexpression of IGFBP-2 in transgenic mice prevents obesity, but depot-specific effects of IGFBP-2 on adipo/lipogenesis are unknown. The present study aimed to investigate whether IGFBP-2 affects adipo/lipogenesis in a depot-specific manner and explore potential mechanisms. METHODS: Following adipocyte characterisation, IGFBP-2 levels were measured from human subcutaneous and visceral preadipocytes, and IGFBP-2 dose-responses were then undertaken with exogenous IGFBP-2 in an in vitro IGF-I-free system to examine adipo/lipogenesis. Following this, both types of adipocytes were transfected with human siRNA IGFBP-2 to assess auto-/para-/intra-crine effects, with and without additional add-back IGFBP-2. To elucidate the potential mechanisms, visceral preadipocytes were treated with either wild-type or Heparin Binding Domain (HBD)-mutant IGFBP-2 (which is unable to bind to cell-surface components), and experiments were also undertaken using Echistatin (an integrin receptor blocker). Outcomes included gene expression profiles, protein levels and phosphorylation and lipid staining. RESULTS: Human visceral adipocytes produced significantly more IGFBP-2 than subcutaneous adipocytes. Subsequent dose-responses to IGFBP-2 demonstrated significant reductions in adipo/lipogenesis in visceral, but not subcutaneous, adipocytes in response to increasing IGFBP-2. Silencing IGFBP-2 resulted in exaggerated adipo/lipogenesis in visceral, but not subcutaneous, adipocytes, an effect completely inhibited by add-back IGFBP-2. These effects occurred in the absence of changes in IGF-I levels. HBD-mutant IGFBP-2 had reduced effects compared with wild-type IGFBP-2. Wild-type IGFBP-2 increased phosphorylation of focal adhesion kinase (FAK) and decreased phosphatase and tensin homolog (PTEN) levels, suggestive of integrin-mediated signalling. Blockade of this signalling, using Echistatin, completely negated the effects of IGFBP-2 on visceral adipo/lipogenesis. CONCLUSION: IGFBP-2 inhibits both adipogenesis and lipogenesis in visceral, but not subcutaneous, adipocytes. This depot-specific impairment appears to be independent of IGF-I and involves cell-surface association of IGFBP-2 and activation of integrin signalling pathways.

IGFBP-2: The dark horse in metabolism and cancer.

The ubiquitous nature of the IGF system, expressed early in embryonic development throughout postnatal and adult life, indicates a key role for this system in human biology. Studies of transgenic mice over-expressing components of the IGF system or mice with disruptions of the same genes have clearly shown that the IGF system plays an important role in vivo. The activity of the IGF ligands, elicited via their receptors and transduced by various intracellular signal pathways, is modulated by the IGFBPs. Among all the IGFBPs, IGFBP-2 has been implicated in the regulation of IGF activity in the nervous system, peripheral tissue and organs. Besides binding to IGFs in the circulation, these IGF-regulatory activities of IGFBP-2 involve interactions with components of the extracellular matrix and cell surface proteoglycans and integrin receptors. In addition to these "local" peri-cellular activities of IGFBP-2, it became evident that IGFBP-2 exerts other key functions within the cell. In the cytoplasm IGFBP-2, most likely in the absence of the IGFs, interacts with regulatory proteins including transcription factors and cytoplasm-nuclear transporters. Within the nucleus IGFBP-2, directly or indirectly, promotes transcriptional activation of specific genes. These intrinsic activities of IGFBP-2 are mediated via specific functional domains. All of these IGFBP-2 activities, intrinsic or dependent on IGFs, contribute to its functional roles in growth/development, metabolism and malignancy as evidenced by studies in IGFBP-2 animal models and also by many in vitro studies. Finally, preclinical studies have demonstrated that IGFBP-2 administration can be beneficial in improving metabolic responses (inhibition of adipogenesis and enhanced insulin sensitivity), while blockade of IGFBP-2 appears to be an effective approach to inhibiting tumor growth and metastasis.

Research priorities in 2012 for the effective management of childhood obesity.

In 2010, the Management Stream of the Australasian Child and Adolescent Obesity Research Network (ACAORN) undertook a Delphi survey asking 'What research questions remain to be addressed in the effective management of child and adolescent obesity?' Members of ACAORN, the Child and Adolescent Obesity Clinics of Australasia Network (CAOCOA-Net) and attendees at the Child Obesity symposium at the annual scientific meeting for the Australian and New Zealand Obesity Society (ANZOS) contributed to three rounds of survey development. Although reasonable concordance in ratings was evident for all 10 questions, 'determining the best strategies for long-term weight management' and 'how best to support the primary healthcare system to achieve these strategies' were clearly identified as the highest research priorities. Other priorities included 'how best to identify the right children with whom to intervene' and 'managing factors which impact on service delivery'. Identifying priority research areas from those working in the field offers the opportunity to stimulate research collaboration and provide justification for funding applications.

Clinical pictures.

A 6 year old girl presents with excessive weight gain. The clincal picture shown is a radiograph of the left hand and wrist.

Normalizing eating behavior reduces body weight and improves gastrointestinal hormonal secretion in obese adolescents.

HYPOTHESIS: Retraining obese adolescents to eat more slowly will lead to beneficial changes in circulating concentrations of gastrointestinal satiety hormones. METHODS: Ghrelin and peptide tyrosine-tyrosine were measured during an oral glucose tolerance test, at baseline and at 12 months during a randomized trial assessing the clinical effectiveness of a device (Mandometer) designed to retrain eating behavior. This computerized scale provided real-time feedback during meals in the intervention arm (n = 14) to slow down the speed of eating. The control group (n = 13) received only standard care aimed at improving lifestyle behavior. The Mandometer elicited greater improvements in weight loss than standard care. RESULTS: Compared with baseline, only those using the Mandometer exhibited lower mean levels of fasting ghrelin (48.14 ± 18.47 vs. 68.45 ± 17.78 pg/ml; P = 0.002) and mean ghrelin area under the curve (72.08 ± 24.11 vs. 125.50 ± 29.72 pg/ml × min; P < 0.001) at 12 months. Absolute mean suppression in ghrelin at 60 min was enhanced (-40.50 ± 21.06 vs. -12.14 ± 19.74 pg/ml × min; P = 0.001). Peptide tyrosine-tyrosine response at 90 min remained unaltered in the standard care arm, whereas those in the Mandometer arm increased (P < 0.001): the mean 90-min response increased by 72 pg/ml [95% confidence interval (CI) 52-92 pg/ml] between baseline and 12 months. In a partial correlation analysis adjusting for change (Δ) in body mass index sd scores, Δ meal duration correlated negatively with Δ absolute suppression in ghrelin at 60 min (r = -0.58; P = 0.037; 95% CI -0.79 to -0.27) and Δ ghrelin area under the curve (r = -0.62; P = 0.025; 95% CI -0.81 to -0.31). CONCLUSIONS: Retraining obese adolescents to eat more slowly has a significant impact on the gastrointestinal hormone response to a carbohydrate load, suggesting that externally modifiable eating behaviors actually regulate the hormonal response to food.

The role of pharmacotherapy in the prevention and treatment of paediatric metabolic syndrome--Implications for long-term health: part of a series on Pediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni.

The metabolic syndrome (MetS) is defined as a clustering of risk factors predisposing to the future development of cardiovascular disease and Type 2 diabetes mellitus (T2DM). Its clinical relevance, above and beyond recognition and treatment of each of the component parts, is still hotly debated--especially within paediatric medicine. Prevention and treatment strategies for adult MetS focus on weight management, as obesity and insulin resistance are known to be at the central axis of the definition, alongside pharmacotherapy of integrally linked conditions such as hypertension and dyslipidaemia. In children and adolescents, however, opportunities for pharmacotherapy are currently limited and interventions aimed at weight management remain the sole treatment paradigm in the majority of cases. This is primarily due to a lack of long-term data relating to the degree of cardiovascular disease and T2DM risk from paediatric MetS, as well as concerns relating to safety and side effect profiles of currently available pharmacotherapies in those who are still growing and developing. Coupled with continuing concern about the recently recognised adverse effects of past and proposed anti-obesity drugs, this indicates that a new era of pharmacotherapy for paediatric MetS is unlikely to be imminent. In fact, the overall paucity of effective current interventions for paediatric MetS is concerning, especially given the fact that approximately 25-33% of all obese paediatric patients likely harbour the condition. It is therefore essential at the present time to concentrate efforts on properly testing the safety and efficacy of currently available products in well-constructed randomised controlled trials in obese adolescents. However, not all obese children and adolescents appear equally at-risk of long-term, weight-related morbidity and a change in emphasis is possibly warranted--one that moves away from simple weight reduction for all and more to a model of reducing long-term risk of cardiovascular disease and T2DM in those at greatest metabolic risk.

Elevated glucose concentrations during an oral glucose tolerance test are associated with the presence of metabolic syndrome in childhood obesity.

AIMS: To investigate whether changes in glucose concentrations during an OGTT in obese children reflect the presence of peripheral insulin resistance and/or cardiovascular risk factors more closely than single measurements of fasting plasma glucose (FPG). METHODS: One hundred and twenty-two obese children attending our Paediatric Obesity Service underwent formal OGTTs, following the measurement of blood pressure and fasting levels of insulin, glucose and lipid profiles in the majority. Fasting insulin was used as a surrogate measure of insulin sensitivity. Three different child-specific definitions for metabolic syndrome were used to identify clustering of cardiovascular risk factors in 65 of these children. RESULTS: In the whole group, 10.7% had IGT but changes in glucose during the OGTT were not influenced by age, sex, pubertal status or raw (or age- and sex-adjusted) body mass index (BMI). During the OGTT, FPG, glucose at 60 min and area under the glucose curve correlated highly with fasting insulin. Children with metabolic syndrome (defined using any of three definitions) had comparable FPG levels to those without metabolic syndrome, but they demonstrated significantly elevated glucose levels at 60 min. On sub-group analysis, obese children with normal carbohydrate metabolism were significantly more likely to have a 1 h glucose level > or = 7.8 mmol/l if they had metabolic syndrome (P = 0.026). CONCLUSIONS: These data suggest that an elevated 1 h post-load glucose measurement is seen in obese children who have a coexistent clustering of cardiovascular risk factors.

Childhood obesity.

The prevalence of childhood obesity continues to increase worldwide. Its presence is associated with significant adverse effects on health including an increased propensity to type II diabetes, cardiovascular, respiratory, and liver disease. In the vast majority of children, obesity is lifestyle-related, yet there is a dearth of evidence on how to best develop effective prevention and treatment strategies. This review outlines the importance of childhood and adolescent growth on long-term health, the definitions used to define obesity in children (along with up-to-date prevalence data), causes and consequences, and aspects of prevention and management.

Characterisation of morbidity in a UK, hospital based, obesity clinic.

AIM: To identify clinical features which predict those most at risk of co-morbidities within an obesity clinic. METHODS: Children attending an obesity clinic had fasting glucose, insulin, and lipids measured prior to a standard oral glucose tolerance test (OGTT). History and examination established birth weight, family history of type 2 diabetes/obesity, pubertal status, and presence of acanthosis nigricans. Central and total fat mass was estimated by bio-impedance. RESULTS: Of the 126 children evaluated, 10.3% (n = 13) had impaired glucose tolerance (IGT); the majority (n = 11) of these would not have been identified on fasting glucose alone. Those with IGT were more likely to have a parental history of type 2 diabetes (relative risk 3.5). IGT was not associated with acanthosis nigricans. Twenty five per cent (n = 19) of those evaluated (n = 75) had evidence of the "metabolic syndrome" (MS). HDL cholesterol and triglyceride levels were related to insulin sensitivity (HOMA-R); HDL cholesterol was also related to birth weight SDS. We observed a trend for those with MS to have a lower birth weight SDS. The severity of obesity did not influence the likelihood of IGT or MS. CONCLUSIONS: Significant numbers of obese children have associated co-morbidities. Analysis of fasting blood glucose samples alone is not satisfactory to adequately evaluate glucose homoeostasis. The overall level of obesity does not predict co-morbidities. Special attention should be given to those with parental diabetes and a history of low birth weight who are more likely to have IGT and abnormal lipid profiles respectively.

Results and complications of laparoscopic cholecystectomy in childhood.

BACKGROUND: The purpose of our study was to evaluate the results and complications of laparoscopic cholecystectomy in a case series of 110 infants. METHODS: Over a 5-year period (1993-98), we performed laparoscopic cholecystectomy in 110 pediatric patients. Surgery was performed at different institutions by three different surgeons. The patient population was composed of 69 girls and 41 boys; their ages ranged from 1 to 16 years (median, 8.5). All of the 110 children had symptomatic cholelithiasis, which was confirmed at ultrasound examination. An associated pathology was present in 27 patients (sickle cell disease in 17 cases, hereditary spherocytosis in seven cases, thalassemia in three); the other 83 infants were affected by idiopathic cholelithiasis. In 107 patients, the operation was performed using four ports; in three patients, it was done using five ports. In three patients, we also performed a concomitant splenectomy. RESULTS: Median duration of simple cholecystectomy was 45 min (range, 25-75) and hospital stay ranged from 1 to 10 days (median, 2). Only 15 children required drainage. We had 17 complications in our series (15.5%), including a gallbladder perforation during dissection in 11 patients, a fall of stones into the abdominal cavity during extraction in one patient, and a trocar orifice infection in the postoperative period in five patients. At a maximum follow-up of five years (range, 1-5), all patients were doing well. CONCLUSION: Laparoscopic cholecystectomy in children seems to be as effective as open surgery in cases of symptomatic cholelithiasis. In pediatric patients more than in adults, an accurate and precise dissection and a sound knowledge of possible congenital biliary abnormalities are essential to avoid any kind of complication.

Results and complications of laparoscopic surgery for pediatric varicocele.

BACKGROUND: The aim of this study was to evaluate the results and complications of laparoscopic varicocelectomy in children. METHODS: Over a 36-month period, 211 children underwent laparoscopic treatment of varicocele. Their ages ranged between 6 and 17 years; the varicocele was located on the left side in 209 cases (99.1%) and was bilateral in 2 (0.9%). In 195 patients the laparoscopic transperitoneal approach was used and in 16 retroperitoneoscopy was used. Thirty children (14.2%) underwent ligation of the veins alone, and 181 (85.8%) underwent ligation of testicular veins and artery. In 15 (7.1%) cases an additional procedure was applied during the same operation. RESULTS: Average operating time was 30 minutes and hospitalization about 24 hours. At an average follow-up of 26 months, there were 19 (9%) postoperative complications: 14 children had a left hydrocele, 3 children a scrotal emphysema, and 2 an umbilical granuloma. There were 5 recurrences of varicocele in our series: 2 (2 of 30, 6.6%) after the Ivanissevitch procedure, and 3 (3 of 181, 1.6%) after Palomo's. Testicular atrophy did not occur in any patient of this series. CONCLUSIONS: This preliminary experience shows that the results of the laparoscopic approach are comparable to those of the open approach. The ligation of testicular veins and artery is preferable to the ligation of the testicular veins alone. Hydrocele seems to be the most frequent postoperative complication and a potential problem, especially in children operated on with the Palomo procedure.

Laparoscopic orchiopexy without division of the spermatic vessels: can it be considered the procedure of choice in cases of intraabdominal testis?

BACKGROUND: Several surgical procedures have been described for the management of nonpalpable testis. Following a vast experience with a complete laparoscopic two-stage Fowler-Stephens procedure, we report our experience with laparoscopic orchiopexy performed without dividing the spermatic vessels. METHODS: Over a 24-month period, 70 boys with nonpalpable testes (72 overall) underwent laparoscopic diagnostic exploration. Twenty patients (27.8%) of this series who showed an intraabdominal testis underwent laparoscopic orchiopexy without sectioning the spermatic vessels. In seven cases, the testis was just proximal to the internal inguinal ring; in 13, it was in the high intraabdominal position. The technique consisted in sectioning the gubernaculum (when present), opening the peritoneum laterally to the spermatic vessels, and mobilizing the testicular vessels and the vas deferens in a retroperitoneal position for 8-10 cm. The testis was then brought down into the scrotum through the internal inguinal ring (11 cases), if this was open, or through a neo-inguinal ring (nine cases) created medially to the epigastric vessels. In every case, we closed the inguinal ring at the end of the operation using one or two detached sutures. RESULTS: Operating time ranged between 40 and 75 min (median, 55). All the testes were successfully brought down into the scrotum. We had only one (5%) intraoperative complication. In the second patient treated with this procedure, there was an iatrogenic rupture of the spermatic vessels due to excessive traction. CONCLUSION: On the basis of our experience, we believe that laparoscopic orchiopexy without division of the spermatic vessels should be the treatment of choice in the management of nonpalpable testes, because it does not affect normal testicular vascularization and is minimally invasive. A blunt dissection and a delicate manipulation of the testis without excessive traction are the best ways to avoid any kind of complication.

Laparoscopic treatment of pediatric varicocele: a multicenter study of the italian society of video surgery in infancy.

PURPOSE: We report preliminary results of a multicenter study of the Italian Society of Video Surgery in Infancy on the laparoscopic treatment of pediatric varicocele. MATERIALS AND METHODS: A total of 161 children 6 to 16 years old (median age 12.5) underwent laparoscopic treatment of varicocele at 6 pediatric surgery divisions. Varicocele was on the left side in 159 cases (98.7%) and bilateral in 2 (1.3%). Two boys had recurrent left varicocele. All children were treated with laparoscopy, including ligation of the spermatic veins only in 28 (17.3%), and ligation of the testicular veins and artery in 133 (82.7%). In 10 boys (6.2%) an additional procedure was done simultaneously, including closure of an apparently patent peritoneal vaginal duct on the right side in 7 and resection of epiploic adhesions between the intestinal loops and abdominal wall from previous appendectomy in the remaining 3. RESULTS: Average operative time was 30 minutes and hospitalization was about 24 hours. At followup there were 13 minor complications (8%), including left hydrocele in 9 children who underwent the Palomo technique, minor scrotal emphysema in 2 and umbilical granuloma in 2. In our series varicocele recurred in 1 boy (3.5%) who underwent ligation of the spermatic veins only and in 3 (2.2%) treated with the Palomo technique. CONCLUSIONS: Our preliminary experience shows that the results of the laparoscopic approach are comparable to those of the open approach. However, the important advantages of laparoscopy over the open approach are its minimal invasiveness and precision of intervention. Moreover, laparoscopy allows treatment of other intra-abdominal pathological conditions using the same anesthesia, as in 10 patients in our series. We believe that ligating the testicular veins and artery is preferable to ligating the testicular veins only, even if the incidence of hydrocele is not negligible after the Palomo procedure.

The accuracy of volumetric bone density measurements in dual x-ray absorptiometry.

New developments in dual x-ray absorptiometry (DXA) allow the performance of high precision anteroposterior (AP) and lateral scans of spinal bone mineral density (BMD, units: g/cm2) without the patient moving from the supine position. Data from both projections may be combined to give an estimate of the true volumetric bone mineral density (VBMD, units: g/cm3) of the lumbar vertebral bodies. This report presents a cadaver study designed to validate DXA measurements of volumetric bone density. Sections of whole lumbar spine were scanned in AP and lateral projections in a water tank to simulate soft tissue. Individual vertebrae were then divided to separate the vertebral body from the neural arch, and vertebral body volume was measured using the displacement of sand. The bone mineral content (BMC) of vertebral bodies and neural arches was measured by ashing at 250 degrees C for 60 hours followed by 500 degrees C for a further 24 hours. The results showed that DXA scanning systematically underestimated ashing data by 14% for AP BMC, 33% for vertebral body BMC, 23% for vertebral body volume, and 12% for VBMD. Despite these significant systematic errors, the DXA measurements and ashing values were highly correlated (r = 0.979-0.992). The results suggested that after allowing for the systematic errors, lateral DXA parameters related closely to true BMC, volume, and VBMD.