Nicola Crabtree

Diagnostic evaluation of bone densitometric size adjustment techniques in children with and without low trauma fractures

SummarySeveral established methods are used to size adjust dual-energy X-ray absorptiometry (DXA) measurements in children. However, there is no consensus as to which method is most diagnostically accurate. All size-adjusted bone mineral density (BMD) values were more diagnostically accurate than non-size-adjusted values. The greatest odds ratio was estimated volumetric BMD for vertebral fracture.IntroductionThe size dependence of areal bone density (BMDa) complicates the use of DXA in children with abnormal stature. Despite several size adjustment techniques being proposed, there is no consensus as to the most appropriate size adjustment technique for estimating fracture risk in children. The aim of this study was to establish whether size adjustment techniques improve the diagnostic ability of DXA in a cohort of children with chronic diseases.MethodsDXA measurements were performed on 450 children, 181 of whom had sustained at least one low trauma fracture. Lumbar spine (L2–L4) and total body less head (TBLH) Z-scores were calculated using different size adjustment techniques, namely BMDa and volumetric BMD for age (bone mineral apparent density (BMAD)); bone mineral content (BMC) and bone area for height; BMC for bone area; BMC for lean mass (adjusted for height); and BMC for bone and body size.ResultsUnadjusted L2–L4 and TBLH BMDa were most sensitive but least specific at distinguishing children with fracture. All size adjustments reduced sensitivity but increased post-test probabilities, from a pre-test probability of 40xa0% to between 58 and 77xa0%. The greatest odds ratio for fracture was L2–L4 BMAD for a vertebral fracture and TBLH for lean body mass (LBM) (adjusted for height) for a long bone fracture with diagnostic odds ratios of 9.3 (5.8–14.9) and 6.5 (4.1–10.2), respectively.ConclusionAll size adjustment techniques improved the predictive ability of DXA. The most accurate method for assessing vertebral fracture was BMAD for age. The most accurate method for assessing long bone fracture was TBLH for LBM adjusted for height.

Pediatric in vivo cross-calibration between the GE Lunar Prodigy and DPX-L bone densitometers

Dual energy x-ray absorptiometry (DXA) machine cross-calibration is an important consideration when upgrading from old to new technology. In a recent cross-calibration study using adult subjects, close agreement between GExa0Lunar DPX-L and GExa0Lunar Prodigy scanners was reported. The aim of this work was to cross-calibrate the two machines for bone and body composition parameters for pediatrics from agexa05xa0years onwards. One-hundredxa0ten healthy volunteers aged 5–20xa0years had total body and lumbar spine densitometry performed on DPX-L and Prodigy densitometers. Cross-calibration was achieved using linear regression and Bland–Altman analysis. There was close agreement between the machines, with r2xa0ranging from 0.85 to 0.99 for bone and body composition parameters. Paired t-tests demonstrated significant differences between machines that were dependent on scan acquisition mode, with the greatest differences reported for the smallest children. At the lumbar spine, Prodigy bone mineral density (BMD) values were on averagexa01.6% higher compared with DPX-L. For the total body, there were no significant differences in BMD; however, there were significant differences in bone mineral content (BMC) and bone area. For small children, the Prodigy measured lower BMC (9.4%) and bone area (5.8%), whereas for larger children the Prodigy measured both higher BMC (3.1%) and bone area (3.0%). A similar contrasting pattern was also observed for the body composition parameters. Prodigy values for lean body mass were higher (3.0%) for small children and lower (0.5%) for larger children, while fat body mass was lower (16.4%) for small children and higher (2.0%) for large children. Cross-calibration coefficients ranged from 0.84 to 1.12 and were significantly different from 1xa0(p<0.0001) for BMC and bone area. Bland–Altman plots showed that within the same scan acquisition modes, the magnitude of the difference increased with body weight. The results from this study suggest that the differences between machines are mainly due to differences in bone detection algorithms and that they vary with body weight and scan mode. In general, for population studies the differences are not clinically significant. However, for individual children being measured longitudinally, cross-over scanning may be required.

Weight regulation and bone mass: a comparison between professional jockeys, elite amateur boxers, and age, gender and BMI matched controls

The aim of this study was to compare bone mass between two groups of jockeys (flat: nxa0=xa014; national hunt: nxa0=xa016); boxers (nxa0=xa014) and age, gender and BMI matched controls (nxa0=xa014). All subjects underwent dual energy X-ray absorptiometry (DXA) scanning for assessment of bone mass, with measurements made of the total body, vertebra L2–4 and femoral neck. Body composition and the relative contribution of fat and lean mass were extrapolated from the results. Data were analysed in accordance with differences in body composition, in particular, height, lean mass, fat mass and age. Both jockey groups were shown to display lower bone mass than either the boxers or control group at a number of sites including total body bone mineral density (BMD) (1.019xa0±xa00.06 and 1.17xa0±xa01.05 vs. 1.26xa0±xa00.01 and 1.26xa0±xa00.06xa0gxa0cm−2 for flat, national hunt, boxer and control, respectively), total body bone mineral content (BMC) less head, L2–4 BMD and femoral neck BMD and BMC (pxa0<xa00.05). Regression analysis revealed that lean mass and height were the primary predictors of total body BMC, although additional group-specific influences were present which reduced bone mass in the flat jockey group and enhanced it in the boxers (R2xa0=xa00.814). Reduced bone mass in jockeys may be a consequence of reduced energy availability in response to chronic weight restriction and could have particular implications for these athletes in light of the high risk nature of the sport. In contrast, the high intensity, high impact training associated with boxing may have conveyed an osteogenic stimulus on these athletes.

Dual-Energy X-Ray Absorptiometry

Early attempts at bone densitometry used conventional x-rays with a step wedge made from an aluminum or ivory phantom included in the field of view as a means of calibration. The bone density was calculated by a visual comparison of the density of the bone and the known densities of the each of the steps on the phantom.

IGFALS Gene Dosage Effects on Serum IGF-I and Glucose Metabolism, Body Composition, Bone Growth in Length and Width, and the Pharmacokinetics of Recombinant Human IGF-I Administration

CONTEXTnAcid labile subunit (ALS) deficiency, caused by IGFALS mutations, is a subtype of primary IGF-I deficiency (PIGFD) and has been associated with insulin resistance (IR) and osteopenia. Whether patients respond to recombinant human IGF-I (rhIGF-I) is unknown.nnnOBJECTIVE AND DESIGNnThis study determined the 14-hour pharmacokinetic response of free and total IGF-I and IGF binding protein 3 (IGFBP-3) to a single sc dose of rhIGF-I (120 μg/kg) in four ALS-deficient patients, compared with severe PIGFD, moderate PIGFD, and controls. Intravenous glucose tolerance tests, fasting blood levels, dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and metacarpal radiogrammetry were performed in the four patients and 12 heterozygous family members.nnnRESULTSnIGF-I and IGFBP-3 increased above baseline (P < .05) for 2.5 hours, returning to baseline 7 hours after rhIGF-I injection. Mean (SD) IGF-I Z-score increased by 2.49 (0.90), whereas IGFBP-3 Z-score increased by 0.57 (0.10) only. IGF-I elimination rates in ALS deficiency were similar, but the IGF-I increment was lower than those for severe PIGFD. Significant gene dosage effects were found for all IGF-I peptides, height, forearm muscle size, and metacarpal width. Bone analysis showed that ALS deficiency creates a phenotype of slender bones with normal size-corrected density. Abnormal glucose handling and IR was found in three of four patients and 6 of 12 carriers.nnnCONCLUSIONSnThese gene dosage effects demonstrate that one functional IGFALS allele is insufficient to maintain normal ALS levels, endocrine IGF-I action, full growth potential, muscle size, and periosteal expansion. Similar gene dosage effects may exist for parameters of IR. Despite similar IGF-I elimination compared with severe PIGFD, ALS-deficient patients cannot mount a similar response. Alternative ways of rhIGF-I administration should be sought.

Amalgamated Reference Data for Size‐Adjusted Bone Densitometry Measurements in 3598 Children and Young Adults—the ALPHABET Study

The increasing use of dual‐energy X‐ray absorptiometry (DXA) in children has led to the need for robust reference data for interpretation of scans in daily clinical practice. Such data need to be representative of the population being studied and be “future‐proofed” to software and hardware upgrades. The aim was to combine all available pediatric DXA reference data from seven UK centers to create reference curves adjusted for age, sex, ethnicity, and body size to enable clinical application, using in vivo cross‐calibration and making data back and forward compatible. Seven UK sites collected data on GE Lunar or Hologic Scanners between 1996 and 2012. Males and females aged 4 to 20 years were recruited (nu2009=u20093598). The split by ethnic group was white 2887; South Asian 385; black Afro‐Caribbean 286; and mixed heritage 40. Scans of the total body and lumbar spine (L1 to L4) were obtained. The European Spine Phantom was used to cross‐calibrate the 7 centers and 11 scanners. Reference curves were produced for L1 to L4 bone mineral apparent density (BMAD) and total body less head (TBLH) and L1 to L4 areal bone mineral density (aBMD) for GE Lunar Prodigy and iDXA (sex‐ and ethnic‐specific) and for Hologic (sex‐specific). Regression equations for TBLH BMC were produced using stepwise linear regression. Scans of 100 children were randomly selected to test backward and forward compatibility of software versions, up to version 15.0 for GE Lunar and Apex 4.1 for Hologic. For the first time, sex‐ and ethnic‐specific reference curves for lumbar spine BMAD, aBMD, and TBLH aBMD are provided for both GE Lunar and Hologic scanners. These curves will facilitate interpretation of DXA data in children using methods recommended in ISCD guidelines. The databases have been created to allow future updates and analysis when more definitive evidence for the best method of fracture prediction in children is agreed.

Impact of UK National Guidelines based on FRAX®– comparison with current clinical practice

Objectiveu2002 To assess whether clinician‐determined treatment intervention thresholds are in line with the assessment of fracture risk provided by FRAX® and treatment recommendations provided by UK guidelines produced by the National Osteoporosis Guidelines Group (NOGG).

Bone status of adolescent girls in Pune (India) compared to age-matched South Asian and white Caucasian girls in the UK.

SummaryUnderprivileged adolescent girls in Pune, India, were shorter and lighter, and had reduced lean body mass (LBM) compared with relatively ‘well off’ age-matched South Asian and white Caucasian girls in the UK. Pune girls had low bone mass for projected bone area (BA) in comparison to their UK counterparts, but they had the appropriate amount of bone mineral content (BMC) for their LBM.PurposeTo determine whether adolescent girls from a low socioeconomic group in Pune, India, who had low dietary calcium intake (449xa0mg/day; range 356–538xa0mg/day) and hypovitaminosis D (median serum 25-hydroxyvitamin D 23.4xa0nmol/l; range 13.5–31.9xa0nmol/l), would have lower lumbar spine (LS) bone mineral apparent density (BMAD), and total body (TB) BMC adjusted for LBM.MethodsDual energy X-ray absorptiometry was used to measure TB and LS BMC, BA and TB LBM in 50 postmenarcheal girls in Pune. These variables were compared with data from 34 South Asian and 82 white Caucasian age-matched girls in the UK.ResultsPune girls were shorter and lighter, and had less LBM for height, compared to both UK groups, and they had later age of menarche than UK Asians. BA-adjusted TB BMC and LS BMAD were lower in Pune girls (mean±SE 1,778±17xa0g; 0.332±0.005xa0g/cm3), compared to the UK South Asians (mean±SE 1,864±18xa0g; 0.355±0.006xa0g/cm3) and UK white Caucasians (mean±SE 1,864±13xa0g; 0.345±0.004xa0g/cm3). In contrast both LS and TB BMC adjusted for TB LBM were not significantly different between the groups.ConclusionPune girls had low bone mass for projected BA relative to UK South Asian and white Caucasian girls, but had the appropriate amount of BMC for their LBM.

Bone Density in the Obese Child: Clinical Considerations and Diagnostic Challenges

The prevalence of obesity in children has reached epidemic proportions. Concern about bone health in obese children, in part, derives from the potentially increased fracture risk associated with obesity. Additional risk factors that affect bone mineral accretion, may also contribute to obesity, such as low physical activity and nutritional factors. Consequences of obesity, such as inflammation, insulin resistance, and non-alcoholic fatty liver disease, may also affect bone mineral acquisition, especially during the adolescent years when rapid increases in bone contribute to attaining peak bone mass. Further, numerous pediatric health conditions are associated with excess adiposity, altered body composition, or endocrine disturbances that can affect bone accretion. Thus, there is a multitude of reasons for considering clinical assessment of bone health in an obese child. Multiple diagnostic challenges affect the measurement of bone density and its interpretation. These include greater precision error, difficulty in positioning, and the effects of increased lean and fat tissue on bone health outcomes. Future research is required to address these issues to improve bone health assessment in obese children.

The relationship between bone mass and body composition in children with hypothalamic and simple obesity

Obesity has been associated with a positive influence on bone mass. This is thought to be due to a mechanical load exerted on the skeleton, together with various hormones and adipocytokines that control appetite and weight, such as leptin, some of which directly affect bone mass. However, there are conflicting reports of the association between fat mass and bone mass in children. Animal studies demonstrate increased bone mass where there is impaired central leptin signalling. Hypothalamic damage can cause abnormal central leptin action, which contributes to the development of obesity.