Lumbar spine bone mineral adaptation: cricket fast bowlers versus controls.

Elite adult male fast bowlers have high lumbar spine bone mineral, particularly on the contralateral side to their bowling arm. It is thought that bone possesses its greatest ability to adapt to loading during adolescence, but it is unknown at what age the greatest changes in lumbar bone mineral and asymmetry develops in fast bowlers. Objectives: This study aims to evaluate the adaptation of the lumbar vertebrae in fast bowlers compared to controls and how this is associated with age. Methods: 91 male fast bowlers and 84 male controls aged 14-24 years had between one and three annual anterior-posterior lumbar spine dual-energy-X-ray absorptiometry scans. Total (L1-L4) and regional ipsilateral and contralateral L3 and L4 (respective to bowling arm) bone mineral density and content (BMD/C) were derived. Multilevel models examined the differences in lumbar bone mineral trajectories between fast bowlers and controls. Results: At L1-L4 BMC and BMD, and contralateral BMD sites, fast bowlers demonstrated a greater negative quadratic pattern to their accrual trajectories than controls. Fast bowlers had greater increases in BMC in L1-L4 between 14 and 24 years of 55% compared with controls (41%). Within vertebra, asymmetry was evident in all fast bowlers and increased by up to 13% in favour of the contralateral side. Conclusions: Lumbar vertebral adaptation to fast bowling substantially increased with age, particularly on the contralateral side. The greatest accrual was during late adolescence and early adulthood, which may correspond with the increasing physiological demands of adult professional sport.

Bone Mineral Density and Vascular Calcification in Children and Young Adults With CKD 4 to 5 or on Dialysis.

Introduction: Older adults with chronic kidney disease (CKD) can have low bone mineral density (BMD) with concurrent vascular calcification. Mineral accrual by the growing skeleton may protect young people with CKD from extraosseous calcification. Our hypothesis was that children and young adults with increasing BMD do not develop vascular calcification. Methods: This was a multicenter longitudinal study in children and young people (5-30 years) with CKD stages 4 to 5 or on dialysis. BMD was assessed by tibial peripheral quantitative computed tomography (pQCT) and lumbar spine dual-energy X-ray absorptiometry (DXA). The following cardiovascular imaging tests were undertaken: cardiac computed tomography for coronary artery calcification (CAC), ultrasound for carotid intima media thickness z-score (cIMTz), pulse wave velocity z-score (PWVz), and carotid distensibility for arterial stiffness. All measures are presented as age-adjusted and sex-adjusted z-scores. Results: One hundred participants (median age 13.82 years) were assessed at baseline and 57 followed up after a median of 1.45 years. Trabecular BMD z-score (TrabBMDz) decreased (P = 0.01), and there was a nonsignificant decrease in cortical BMD z-score (CortBMDz) (P = 0.09). Median cIMTz and PWVz showed nonsignificant increase (P = 0.23 and P = 0.19, respectively). The annualized increase in TrabBMDz (ΔTrabBMDz) was an independent predictor of cIMTz increase (R 2 = 0.48, ß = 0.40, P = 0.03). Young people who demonstrated statural growth (n = 33) had lower ΔTrabBMDz and also attenuated vascular changes compared with those with static growth (n = 24). Conclusion: This hypothesis-generating study suggests that children and young adults with CKD or on dialysis may develop vascular calcification even as their BMD increases. A presumed buffering capacity of the growing skeleton may offer some protection against extraosseous calcification.

Naturally occurring stable calcium isotope ratios are a novel biomarker of bone calcium balance in chronic kidney disease.

Dysregulated calcium homeostasis is common in chronic kidney disease and causally associated with disorders of bone mineralization. However, radiological measures and biomarkers do not allow accurate evaluation of bone calcium balance. Non-radioactive calcium isotopes, 42Ca and 44Ca, are present in our diet and sequestered into body compartments following principles of kinetic isotope fractionation. Isotopically light 42Ca is preferentially incorporated into bone, while heavier 44Ca is excreted. The ratio (44/42Caserum) increases when bone formation exceeds resorption and vice versa, reflecting bone calcium balance. We measured these calcium isotopes by inductively coupled plasma mass-spectrometry in blood, urine and feces of 42 children with chronic kidney disease and 92 receiving dialysis therapy. We compared the isotope ratios with bone biomarkers and determined total bone mineral content by dual-energy x-ray absorptiometry and peripheral quantitative CT expressed as age-adjusted z-scores. The 44/42Caserum ratio positively correlated with serum calcium, 25-hydroxyvitamin D and alkaline phosphatases and inversely with serum parathyroid hormone and other bone resorption markers. The 44/42Caserum ratio positively correlated with age-adjusted z-scores of tibial trabecular bone mineral density and total bone mineral content measured by peripheral quantitative CT, and hip bone mineral density measured by dual-energy X-ray absorptiometry. Significant and independent predictors of total bone mineral content, measured by, were the 44/42Caserum ratio and parathyroid hormone. The 44/42Caserum ratio, repeated after four weeks, highly correlated with baseline values. When adjusted for calcium-containing medications and kidney impairment, the 44/42Caserum ratio in patients receiving dialysis was 157% lower than that of age-matched children and 29% lower than levels in elderly women with osteoporosis, implying significantly lower bone mineral content. Thus, calcium isotope ratios may provide a novel, sensitive and non-invasive method of assessing bone calcium balance in chronic kidney disease.

Digital health interventions for osteoporosis and post-fragility fracture care.

The growing burden from osteoporosis and fragility fractures highlights a need to improve osteoporosis management across healthcare systems. Sub-optimal management of osteoporosis is an area suitable for digital health interventions. While fracture liaison services (FLSs) are proven to greatly improve care for people with osteoporosis, such services might benefit from technologies that enhance automation. The term 'Digital Health' covers a variety of different tools including clinical decision support systems, electronic medical record tools, patient decision aids, patient apps, education tools, and novel artificial intelligence (AI) algorithms. Within the scope of this review are AI solutions that use algorithms within health system registries to target interventions. Clinician-targeted, patient-targeted, or system-targeted digital health interventions could be used to improve management and prevent fragility fractures. This review was commissioned by The Royal Osteoporosis Society and Bone Research Academy during the production of the 2020 Research Roadmap (https://theros.org.uk), with the intention of identifying gaps where targeted research funding could lead to improved patient health. We explore potential uses of digital technology in the general management of osteoporosis. Evidence suggests that digital technologies can support multidisciplinary teams to provide the best possible patient care based on current evidence and to support patients in self-management. However, robust randomised controlled studies are still needed to assess the effectiveness and cost-effectiveness of these technologies.

A Three-Year Longitudinal Study Comparing Bone Mass, Density, and Geometry Measured by DXA, pQCT, and Bone Turnover Markers in Children with PKU Taking L-Amino Acid or Glycomacropeptide Protein Substitutes.

In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm. AIMS: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein glycomacropeptide substitutes (CGMP-AA) as their main protein source. METHODOLOGY: A total of 48 subjects completed the study, 19 subjects in the L-AA group (median age 11.1, range 5-16 years) and 29 subjects in the CGMP-AA group (median age 8.3, range 5-16 years). The CGMP-AA was further divided into two groups, CGMP100 (median age 9.2, range 5-16 years) (n = 13), children taking CGMP-AA only and CGMP50 (median age 7.3, range 5-15 years) (n = 16), children taking a combination of CGMP-AA and L-AA. Dual X-ray absorptiometry (DXA) was measured at enrolment and 36 months, peripheral quantitative computer tomography (pQCT) at 36 months only, and serum blood and urine bone turnover markers (BTM) and blood bone biochemistry at enrolment, 6, 12, and 36 months. RESULTS: No statistically significant differences were found between the three groups for DXA outcome parameters, i.e., BMDa (L2-L4 BMDa g/cm2), bone mineral apparent density (L2-L4 BMAD g/cm3) and total body less head BMDa (TBLH g/cm2). All blood biochemistry markers were within the reference ranges, and BTM showed active bone turnover with a trend for BTM to decrease with increasing age. CONCLUSIONS: Bone density was clinically normal, although the median z scores were below the population mean. BTM showed active bone turnover and blood biochemistry was within the reference ranges. There appeared to be no advantage to bone density, mass, or geometry from taking a macropeptide-based protein substitute as compared with L-AAs.

Opportunistic diagnosis of osteoporosis, fragile bone strength and vertebral fractures from routine CT scans; a review of approved technology systems and pathways to implementation.

Osteoporosis causes bones to become weak, porous and fracture more easily. While a vertebral fracture is the archetypal fracture of osteoporosis, it is also the most difficult to diagnose clinically. Patients often suffer further spine or other fractures, deformity, height loss and pain before diagnosis. There were an estimated 520,000 fragility fractures in the United Kingdom (UK) in 2017 (costing £4.5 billion), a figure set to increase 30% by 2030. One way to improve both vertebral fracture identification and the diagnosis of osteoporosis is to assess a patient's spine or hips during routine computed tomography (CT) scans. Patients attend routine CT for diagnosis and monitoring of various medical conditions, but the skeleton can be overlooked as radiologists concentrate on the primary reason for scanning. More than half a million CT scans done each year in the National Health Service (NHS) could potentially be screened for osteoporosis (increasing 5% annually). If CT-based screening became embedded in practice, then the technique could have a positive clinical impact in the identification of fragility fracture and/or low bone density. Several companies have developed software methods to diagnose osteoporosis/fragile bone strength and/or identify vertebral fractures in CT datasets, using various methods that include image processing, computational modelling, artificial intelligence and biomechanical engineering concepts. Technology to evaluate Hounsfield units is used to calculate bone density, but not necessarily bone strength. In this rapid evidence review, we summarise the current literature underpinning approved technologies for opportunistic screening of routine CT images to identify fractures, bone density or strength information. We highlight how other new software technologies have become embedded in NHS clinical practice (having overcome barriers to implementation) and highlight how the novel osteoporosis technologies could follow suit. We define the key unanswered questions where further research is needed to enable the adoption of these technologies for maximal patient benefit.

Growth and Body Composition in PKU Children-A Three-Year Prospective Study Comparing the Effects of L-Amino Acid to Glycomacropeptide Protein Substitutes.

Protein quality and quantity are important factors in determining lean body (muscle) mass (LBM). In phenylketonuria (PKU), protein substitutes provide most of the nitrogen, either as amino acids (AA) or glycomacropeptide with supplementary amino acids (CGMP-AA). Body composition and growth are important indicators of long-term health. In a 3-year prospective study comparing the impact of AA and CGMP-AA on body composition and growth in PKU, 48 children were recruited. N = 19 (median age 11.1 years, range 5-15 years) took AA only, n = 16 (median age 7.3 years, range 5-15 years) took a combination of CGMP-AA and AA, (CGMP50) and 13 children (median age 9.2 years, range 5-16 years) took CGMP-AA only (CGMP100). A dual energy X-ray absorptiometry (DXA) scan at enrolment and 36 months measured LBM, % body fat (%BF) and fat mass (FM). Height was measured at enrolment, 12, 24 and 36 months. No correlation or statistically significant differences (after adjusting for age, gender, puberty and phenylalanine blood concentrations) were found between the three groups for LBM, %BF, FM and height. The change in height z scores, (AA 0, CGMP50 +0.4 and CGMP100 +0.7) showed a trend that children in the CGMP100 group were taller, had improved LBM with decreased FM and % BF but this was not statistically significant. There appeared to be no advantage of CGMP-AA compared to AA on body composition after 3-years of follow-up. Although statistically significant differences were not reached, a trend towards improved body composition was observed with CGMP-AA when it provided the entire protein substitute requirement.

Increased prevalence of fractures in inadequately transfused and chelated Indian children and young adults with beta thalassemia major.

INTRODUCTION: In patients with beta thalassemia major, inadequate transfusion and chelation may compromise bone health and increase risk of fractures. The objective of this study was to describe the prevalence of fractures in Indian inadequately transfused and chelated children, adolescents and young adults with beta thalassemia major. METHODS: We studied 179 patients with beta thalassemia (3.6-28.3 years; 105 boys). Medical, transfusion, chelation and fracture history were recorded. Vertebral fracture assessment (VFA) was performed using lateral spine images acquired using the GE Lunar iDXA (Wisconsin, MD). Fractures were classified according to an adapted semi-quantitative method. RESULTS: History of non-traumatic long bone fractures was observed in 21% patients (n = 37); there were significantly greater (p < 0.05) number of males (n = 30) than females (n = 15). The 21% fracture prevalence in the present study is higher than the reported fractures of 9% in healthy Indian children and adolescents. The prevalence of vertebral fractures was 4.5% (n = 8) in the study group. Of those with fractures, four patients had both long bone and vertebral fractures, and (any, long bone or vertebral fractures) sixteen patients had more than 1 fracture; eleven patients had 2 fractures, four patients had 3 fractures and one patient had 5 fractures. Thus, in 179 patients, there were a total of 68 single fractures which translates to 307 fractures per 10,000 patient years. CONCLUSION: This study found increased prevalence of non-traumatic long bone and vertebral fractures in children and adolescents with thalassemia major.

Assessment of Bone Density by DXA in Poorly Controlled Children With ß-Thalassemia: Correction for Hepatic Iron Overload by Manual Analysis.

INTRODUCTION: Beta thalassemia major (BTM) is characterized by anemia and iron overload, especially with inadequate chelation therapy. Dual energy x-ray absorptiometry software (DXA) may misanalyse bone measurements due to iron deposition in organs such as the liver. Our objective was to study difference between the posterior-anterior spine measurements of bone mineral content (BMC), area (BA) and density (BMD) in poorly chelated beta thalassemia patients with and without inclusion of the liver in the DXA analysis. METHODS: We studied hemoglobin and serum ferritin concentrations in 208 patients with BTM (children n = 177, young adults n = 31). Posteroanterior spine measurements BMC, BA and areal BMD were performed using a GE iDXA. Using the tissue point typing feature (EnCore software, version 16), analysis was carried out including and excluding (manually) the iron overloaded liver. Machine generated Z-scores of L1-L4 BMD were used for analysis. RESULTS: The mean age of the study group was 12.9 ± 5.4 yr. Mean hemoglobin and serum ferritin concentrations were 8.0 ± 1.7 g/dl and 2256.9 ± 1978.0 ng/ml, respectively. The mean BMC, BA, and aBMD at the lumbar spine were 23.2 ± 11.4 g, 29.9 ± 8.5 cm2 and 0.736 ± 0.173 g/cm2 respectively with inclusion of liver that is standard machine analysis. After the liver was excluded from the analysis, the mean BMC, BA, and aBMD were 23.9 ± 11.6 g, 30.0 ± 8.6 cm2 and 0.757 ±0.173 g/cm2, respectively and the BMC and aBMD were significantly greater (p < 0.05). Mean BMD Z-score was -1.5 ± 1.2, which significantly (p < 0.05) improved to -1.3 ± 1.2 after exclusion of the liver from the analysis. CONCLUSION: In poorly chelated patients with thalassemia, inclusion of the iron-overloaded liver in the tissue analysis may exaggerate the deficit in bone parameters. Iron overloaded tissues need to be manually excluded during analysis of the PA spine.

Routine serum biomarkers, but not dual-energy X-ray absorptiometry, correlate with cortical bone mineral density in children and young adults with chronic kidney disease.

BACKGROUND: Biomarkers and dual-energy X-ray absorptiometry (DXA) are thought to be poor predictors of bone mineral density (BMD). The Kidney Disease: Improving Global Outcomes guidelines suggest using DXA if the results will affect patient management, but this has not been studied in children or young adults in whom bone mineral accretion continues to 30 years of age. We studied the clinical utility of DXA and serum biomarkers against tibial cortical BMD (CortBMD) measured by peripheral quantitative computed tomography, expressed as Z-score CortBMD, which predicts fracture risk. METHODS: This was a cross-sectional multicentre study in 26 patients with CKD4 and 5 and 77 on dialysis. RESULTS: Significant bone pain that hindered activities of daily living was present in 58%, and 10% had at least one low-trauma fracture. CortBMD and cortical mineral content Z-scores were lower in dialysis compared with CKD patients (P = 0.004 and P = 0.02). DXA BMD hip and lumbar spine Z-scores did not correlate with CortBMD or biomarkers. CortBMD was negatively associated with parathyroid hormone (PTH; r = -0.44, P < 0.0001) and alkaline phosphatase (ALP; r = -0.22, P = 0.03) and positively with calcium (Ca; r = 0.33, P = 0.001). At PTH <3 times upper limit of normal, none of the patients had a CortBMD below -2 SD (odds ratio 95% confidence interval 7.331 to infinity). On multivariable linear regression PTH (ß = -0.43 , P < 0.0001), ALP (ß = -0.36, P < 0.0001) and Ca (ß = 0.21, P = 0.005) together predicted 57% of variability in CortBMD. DXA measures did not improve this model. CONCLUSIONS: Taken together, routinely used biomarkers, PTH, ALP and Ca, but not DXA, are moderate predictors of cortical BMD. DXA is not clinically useful and should not be routinely performed in children and young adults with CKD 4-5D.

The UK Biobank imaging enhancement of 100,000 participants: rationale, data collection, management and future directions.

UK Biobank is a population-based cohort of half a million participants aged 40-69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world's largest multi-modal imaging study, with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future directions.

Diagnostic performance of morphometric vertebral fracture analysis (MXA) in children using a 33-point software program.

BACKGROUND: There is significant inter and intraobserver variability in diagnosing vertebral fractures in children. PURPOSE: We aimed to evaluate the diagnostic accuracy of morphometric vertebral fracture analysis (MXA) using a 33-point software program designed for adults, on dual-energy x-ray absorptiometry (DXA) images of children. MATERIALS AND METHODS: Lateral spine DXA images of 420 children aged between 5 and 18 years were retrospectively reviewed. Vertebral fracture assessment (VFA) by an expert pediatric radiologist using Genant's semiquantitative scoring system served as the gold standard. All 420 DXA scans were analyzed by a trained radiographer, using semi-automated software (33-point morphometry). VFA of a random sample of 100 DXA was performed by an experienced pediatric clinical scientist. MXA of a random sample of 30 DXA images were analyzed by three pediatric radiologists and the pediatric clinical scientist. Diagnostic accuracy and inter and intraobserver agreement (kappa statistics) were calculated. RESULTS: Overall sensitivity, specificity, false positive (FP) and false negative (FN) rates for the radiographer using the MXA software were 80%, 90%, 10%, and 20% respectively and for mild fractures alone were 46%, 92%, 8%, and 54% respectively. Overall sensitivity, specificity, FP, and FN rates for the four additional observers using MXA were 89%, 79%, 21%, and 11% respectively and for mild fractures alone were 36%, 86%, 14%, and 64% respectively. Agreement between two expert observers was fair to good for VFA and MXA [kappa = 0·29 to 0·76 (95% CI: 0·17-0·88) and 0·29 to 0·69 (95% CI: 0·17-0·83)] respectively. CONCLUSION: MXA using a 33-point technique developed for adults is not a reliable method for the identification of mild vertebral fractures in children. A pediatric standard is required which not only incorporates specific vertebral body height ratios but also the age-related physiological changes in vertebral shape that occur throughout childhood.

Older age at initiation of antiretroviral therapy predicts low bone mineral density in children with perinatally-infected HIV in Zimbabwe.

BACKGROUND: Perinatally-acquired HIV infection commonly causes stunting in children; how this affects bone and muscle development is unclear. We investigated differences in bone and muscle mass and muscle function between children with HIV (CWH) and uninfected children. SETTING: Cross-sectional study of CWH (6-16 years) receiving antiretroviral therapy (ART) for >6 months and similar aged children testing HIV-negative at primary health clinics in Zimbabwe. METHODS: From Dual-energy X-ray Absorptiometry (DXA) we calculated total-body less-head (TBLH) Bone Mineral Content (BMC) for lean mass adjusted-for-height (TBLH-BMCLBM) Z-scores, and lumbar spine (LS) Bone Mineral Apparent Density (BMAD) Z-scores. RESULTS: The 97 CWH were older (mean age 12.7 vs. 10.0 years) and taller (mean height 142 cm vs. 134 cm) than 77 uninfected. However, stunting (height-for-age Z-score ≤ -2) was more prevalent in CWH (35% vs. 5%, p < 0.001). Among CWH, 15% had low LS-BMAD (Z-score ≤ -2) and 13% low TBLH-BMCLBM, vs. 1% and 3% respectively in those uninfected (both p ≤ 0.02). After age, sex, height and puberty adjustment, LS-BMAD was 0.33 SDs (95%CI -0.01, 0.67; p = 0.06) lower in CWH, with no differences by HIV status in TBLH-BMCLBM, lean mass (0.11 [-0.03, 0.24], p = 0.11) or grip strength (0.05 [-0.16, 0.27], p = 0.62). However, age at ART initiation was correlated with both LS-BMAD Z-score (r = -0.33, p = 0.001) and TBLH-BMCLBM Z-score (r = -0.23, p = 0.027); for each year ART initiation was delayed a 0.13 SD reduction in LS-BMAD was seen. CONCLUSION: Size-adjusted low bone density is common in CWH. Delay in initiating ART adversely affects bone density. Findings support immediate ART initiation at HIV diagnosis.

Bone density in children: what are we measuring?

The measurement of bone density is a frequent request in the assessment of children with concerns about bone health due to chronic disease or recurrent fractures. Dual energy X-ray absorptiometry (DXA) remains the recommended modality and is widely available. However, the interpretation and reporting of results in growing individuals needs to be undertaken by individuals who are familiar with scanning children and the potential pitfalls.

Increased central adiposity and decreased subcutaneous adipose tissue 11ß-hydroxysteroid dehydrogenase type 1 are associated with deterioration in glucose tolerance-A longitudinal cohort study.

OBJECTIVE AND CONTEXT: Increasing adiposity, ageing and tissue-specific regeneration of cortisol through the activity of 11ß-hydroxysteroid dehydrogenase type 1 have been associated with deterioration in glucose tolerance. We undertook a longitudinal, prospective clinical study to determine if alterations in local glucocorticoid metabolism track with changes in glucose tolerance. DESIGN, PATIENTS, AND MEASUREMENTS: Sixty-five overweight/obese individuals (mean age 50.3 ± 7.3 years) underwent oral glucose tolerance testing, body composition assessment, subcutaneous adipose tissue biopsy and urinary steroid metabolite analysis annually for up to 5 years. Participants were categorized into those in whom glucose tolerance deteriorated ("deteriorators") or improved ("improvers"). RESULTS: Deteriorating glucose tolerance was associated with increasing total and trunk fat mass and increased subcutaneous adipose tissue expression of lipogenic genes. Subcutaneous adipose tissue 11ß-HSD1 gene expression decreased in deteriorators, and at study completion, it was highest in the improvers. There was a significant negative correlation between change in area under the curve glucose and 11ß-HSD1 expression. Global 11ß-HSD1 activity did not change and was not different between deteriorators and improvers at baseline or follow-up. CONCLUSION: Longitudinal deterioration in metabolic phenotype is not associated with increased 11ß-HSD1 activity, but decreased subcutaneous adipose tissue gene expression. These changes may represent a compensatory mechanism to decrease local glucocorticoid exposure in the face of an adverse metabolic phenotype.

Cumulative radiation exposure from medical imaging and associated lifetime cancer risk in children with osteogenesis imperfecta.

OBJECTIVES: To estimate the cumulative effective dose of radiation (E) and additional lifetime attributable risk (LAR) of cancer from ionizing radiation in children with osteogenesis imperfecta (OI), who require frequent imaging for fractures and bone densitometry (DXA) surveillance. Also, to evaluate the pattern of long bone fractures. METHODS: We reviewed all imaging (x-rays, DXA and computed tomography [CT]) conducted in a cohort of children with OI with a minimum observation period of 5 years. For each image, E was estimated using age-dependent local data, and LAR of cancer was extrapolated. LAR and fracture data were compared among children with mild, moderate and severe OI. LAR was allocated to cancer risk categories, and the moderate risk group (1 in 1000 to 1 in 100) was evaluated further. RESULTS: Results from 106 children with OI (50% females, 5747 images) are presented, with a median (range) observation period of 11.7 (5.2-15.6) years. CT accounted for 0.8% of total imaging procedures but contributed to 66% of total E. The overall LAR of cancer was minimal, averaging an additional 8.8 cases per 100,000 exposed patients (0.8-403). LAR was significantly lower in children with mild OI compared to those with moderate (p = 0.006) and severe OI (p = 0.001). All patients with a moderate LAR of cancer (n = 8) had undergone CT scans and 88% had scoliosis or vertebral fractures. The cohort experienced 412 long bone fractures, with the most common site being the femur (26.5%). OI severity correlated positively with long bone fracture rates (p < 0.001). CONCLUSIONS: When compared to baseline LAR of cancer (50%) the additional cancer risk from ionizing radiation imaging in our paediatric OI cohort was small (0.0088%). To reduce additional cancer risk, we recommend replacing spinal x-rays with vertebral fracture assessments on DXA and exercising caution with CT imaging.

Bone Mineral Density Corrected for Size in Childhood Leukaemia Survivors Treated with Haematopoietic Stem Cell Transplantation and Total Body Irradiation.

BACKGROUND: Childhood leukaemia survivors treated with haematopoietic stem cell transplantation and total body irradiation (HSCT-TBI) have multiple risk factors for reduced bone mineral density (BMD) and growth failure; hence, BMD assessment must take body size into consideration. This study aimed to evaluate size-corrected BMD in leukaemia survivors treated with and without HSCT-TBI. METHODS: Childhood leukaemia survivors treated with HSCT-TBI (n = 35), aged 17.3 (10.5-20.9) years, were compared with those treated with chemotherapy only, (n = 16) aged 18.5 (16.1-20.9) years, and population references. Outcome measures included anthropometric measurements and BMD by dual-energy X-ray absorptiometry. BMD was corrected for size as bone mineral apparent density (BMAD). Statistical analysis was performed by 1- and 2-sample t tests as well as regression analysis (5% significance). RESULTS: HSCT-TBI survivors were lighter and shorter with reduced spinal heights compared with chemotherapy-only subjects and population references. Compared with population references, HSCT-TBI survivors showed lower BMD standard deviation scores (SDS) (p = 0.008), but no difference in BMAD-SDS, and chemotherapy-only survivors showed no differences in neither BMD-SDS nor BMAD-SDS. All HSCT-TBI participants with BMD-SDS <-2 had BMAD-SDS >-2. BMAD-SDS was negatively associated with age (r = -0.38, p = 0.029) in HSCT-TBI survivors. CONCLUSIONS: Size-corrected BMD are normal in HSCT-TBI survivors in young adulthood, but may reduce overtime. BMD measurements should be corrected for size in these patients to be clinically meaningful.

Efficacy and treatment costs of zoledronate versus pamidronate in paediatric osteoporosis.

Intravenous pamidronate has been used in the treatment of osteogenesis imperfecta (OI) in children for over 20 years. The more potent zoledronate is an attractive alternative as it is administered less frequently. This study compares the clinical efficacy of intravenous pamidronate (1.5 mg/kg/day over 2 days, every 3 months) versus zoledronate (0.05 mg/kg/dose every 6 months) in 40 children (20 per group) with mild to moderate OI and the treatment costs of the two drugs in a tertiary centre for children with osteoporosis. Lumbar spine bone mineral density and fracture rate did not differ between drug groups following 1 and 2 years of treatment, respectively. Total cost per treatment course per patient was £1157 for pamidronate and £498 for zoledronate. Therefore, zoledronate is a considerably cheaper alternative to pamidronate with comparable efficacy, resulting in substantial annual savings for healthcare providers and a more convenient option for patients due to fewer hospital visits.