The impact of type 1 diabetes mellitus in childhood on academic performance: A matched population-based cohort study.

BACKGROUND AND OBJECTIVE: The impact of type 1 diabetes mellitus (T1D) on academic performance is inconclusive. This study aims to compare scholastic performance and high-school completion in young people hospitalized with T1D compared to matched peers not hospitalized with diabetes. RESEARCH DESIGN: Retrospective case-comparison cohort study. METHOD: A population-level matched case-comparison study of people aged ≤18 hospitalized with T1D during 2005-2018 in New South Wales, Australia using linked health-related and education records. The comparison cohort was matched on age, gender, and residential postcode. Generalized linear mixed modeling examined risk of school performance below the national minimum standard (NMS) and generalized linear regression examined risk of not completing high school for young people hospitalized with T1D compared to peers. Adjusted relative risks (ARR) were calculated. RESULTS: Young females and males hospitalized with T1D did not have a higher risk of not achieving the NMS compared to peers for numeracy (ARR: 1.19; 95%CI 0.77-1.84 and ARR: 0.74; 95%CI 0.46-1.19) or reading (ARR: 0.98; 95%CI 0.63-1.50 and ARR: 0.85; 95%CI 0.58-1.24), respectively. Young T1D hospitalized females had a higher risk of not completing year 11 (ARR: 1.73; 95%CI 1.19-2.53) or 12 (ARR: 1.65; 95%CI 1.17-2.33) compared to peers, while hospitalized T1D males did not. CONCLUSIONS: There was no difference in academic performance in youth hospitalized with T1D compared to peers. Improved glucose control and T1D management may explain the absence of school performance decrements in students with T1D. However, females hospitalized with T1D had a higher risk of not completing high school. Potential associations of this increased risk, with attention to T1D and psycho-social management, should be investigated.

Global consensus on nutritional rickets: Implications for Australia.

In 2016, a global consensus on the prevention, diagnosis and management of nutritional rickets was published. The bone and mineral working group of the Australasian Paediatric Endocrine Group provides a summary and highlights differences to previous Australian and New Zealand (ANZ) guidelines on vitamin D deficiency and their implications for clinicians. Key points are: (i) The International Consensus document is focused on nutritional rickets, whereas the ANZ guidelines were focused on vitamin D deficiency. (ii) Definitions for the interpretation of 25-hydroxy vitamin D (25OHD) levels do not differ between statements. (iii) The global consensus recommends that routine 25OHD screening should not be performed in healthy children and recommendations for vitamin D supplementation are not based solely on 25OHD levels. The Australasian Paediatric Endocrine Group bone and mineral working group supports that screening for vitamin D deficiency should be restricted to populations at risk. (iv) Recommendations from the global consensus for vitamin D dosages for the therapy of nutritional rickets (diagnosed based on history, physical examination, biochemical testing and a confirmation by X-rays) are higher than in ANZ publications. (v) The global consensus recommends the implementation of public health strategies such as universal supplementation with vitamin D from birth to 1 year of age and food fortification. We conclude that updated global recommendations for therapy of nutritional rickets complement previously published position statements for Australia and New Zealand. Screening, management and the implementation of public health strategies need to be further explored for Australia.

Sydney Diabetes centre's experience of the Australian Government's roll out of subsidised continuous glucose monitoring for children with type 1 diabetes mellitus.

AIM: To determine patient/carer expectations of continuous glucose monitoring (CGM) and short-term satisfaction, to assess the efficacy of CGM in improving: fear of hypoglycaemia and glycaemic control (HbA1c , ketosis, hypoglycaemia) and to determine time requirements of diabetes clinic staff in commencing and administering CGM. METHODS: We assessed CGM-naïve patients starting on CGM at a Sydney Diabetes Centre following the introduction of a nationwide government subsidy for CGM. A standardised questionnaire was administered collecting demographic and glycaemic information in addition to Likert scale assessment of expectations and satisfaction. Clinic staff reported time dedicated to CGM education, commencement and follow-up. RESULTS: A total of 55 patients or parents/carers completed baseline questionnaires, with 37 completing a 3-month follow-up questionnaire. There were high expectations of CGM prior to commencement and high satisfaction ratings on follow-up. CGM improved fear of hypoglycaemia, and total daily insulin dose increased after commencement of CGM. There was a trend towards lower HbA1c that was not statistically significant and no statistically significant reduction in ketosis or hypoglycaemia. Comments were mostly positive, with some concern raised regarding technical issues and a lack of subsidy after 21 years of age. Staff time requirements were substantial, with an estimated average of 7.7 h per patient per year. CONCLUSIONS: Patients and families have high expectations of CGM, and satisfaction levels are high in the short term. Total insulin delivery increased after CGM commencement. Time requirements by staff are substantial but are worthwhile if families' overall satisfaction levels are high.

Consensus guidelines on the use of bisphosphonate therapy in children and adolescents.

Bisphosphonate therapy is the mainstay of pharmacological intervention in young people with skeletal fragility. The evidence of its use in a variety of conditions remains limited despite over three decades of clinical experience. On behalf of the Australasian Paediatric Endocrine Group, this evidence-based consensus guideline presents recommendations and discusses the graded evidence (using the GRADE system) for these recommendations. Primary bone fragility disorders such as osteogenesis imperfecta are considered separately from osteoporosis secondary to other clinical conditions (such as cerebral palsy, Duchenne muscular dystrophy). The use of bisphosphonates in non-fragility conditions, such as fibrous dysplasia, avascular necrosis, bone cysts and hypercalcaemia, is also discussed. While these guidelines provide an evidence-based approach where possible, further research is required in all clinical applications in order to strengthen the recommendations made.

A pilot randomized controlled trial of a post-discharge program to support emerging adults with type 1 diabetes mellitus transition from pediatric to adult care.

AIMS: There is a paucity of randomized controlled trials (RCT) examining transition from pediatric to adult care in type 1 diabetes mellitus (T1DM). This study aimed to determine if transition in T1DM is more effective with a comprehensive transition program (CTP) compared with standard clinical practice (SCP). METHODS: This RCT recruited as young people left pediatric diabetes services. The trial co-ordinator provided CTP participants with standardized telephone communication support at week 1, and 3, 6, and 12 months post-discharge from pediatric care. SCP participants were briefly contacted at 6 and 12 months post-discharge to confirm transfer status; they received no other post-discharge contact as per usual practice. At 12 months, the primary outcomes were engagement and retention in the adult service and secondary outcomes included hemoglobin A1c (HbA1c), diabetes-related hospitalizations, microvascular complication appearance, and global self-worth. RESULTS: Most CTP participants (11/14) and all SCP (12/12) participants (P = 0.2) transferred to an adult diabetes service; the median time to transfer was 14-15 wk. Overall, participants' frequency of adult diabetes service visits was sub-optimal but their retention in adult care was high. The only group difference was a higher HbA1c at baseline and follow-up in the CTP group. However, a general linear model found that follow-up HbA1c increased by 1.2% for each percentage increase in baseline HbA1c [95% confidence interval (0.4, 1.9; P = 0.01)], independent of treatment group. CONCLUSIONS: Despite the challenges in recruiting adequate numbers, these findings provide valuable insights for future T1DM transition RCTs that are needed to build a more solid evidence-base in this field.

Single High-Dose Oral Vitamin D3 Therapy (Stoss): A Solution to Vitamin D Deficiency in Children With Inflammatory Bowel Disease?

OBJECTIVES: Vitamin D deficiency is common in children with inflammatory bowel disease (IBD). The aim of this study was to determine the safety and efficacy of stoss therapy on vitamin D levels during a period of 6 months in children with IBD and vitamin D deficiency (<50 nmol/L). METHODS: A retrospective chart review was undertaken, focusing upon children managed in the IBD clinic at Sydney Children's Hospital between 2006 and 2010. Those with a 25-hydroxyvitamin D (25-OHD) level <50 nmol/L and those who received stoss therapy were included in this study. RESULTS: A total of 76 children received stoss therapy. There was a significant and sustained increase in 25-OHD levels at all of the time points compared with baseline (40.8 ±â€Š7.5 nmol/L), 1 month (145.6 ±â€Š51.8 nmol/L), 3 months (87.1 ±â€Š28.4 nmol/L), and 6 months 69.2 ±â€Š31.3 nmol/L). There were no significant changes in serum calcium, phosphate, or parathyroid hormone at any time points. CONCLUSIONS: Stoss therapy safely and effectively achieved and maintained a level of 25-OHD >50 nmol/L during 6 months in these children with IBD. Further prospective studies are now required to confirm this finding and establish whether this intervention has other benefits.

Population-based incidence of diabetes in Australian youth aged 10-18 yr: increase in type 1 diabetes but not type 2 diabetes.

BACKGROUND: Global incidence of childhood type 2 diabetes has increased, with a greater rise amongst certain ethnic groups. OBJECTIVES: To examine the change in the incidence of type 1 and type 2 diabetes in Australian youth, aged 10-18 yr, in New South Wales, Australia. METHODS: Prospective population-based incidence study (2001-2008). Primary case ascertainment was from the Australasian Paediatric Endocrine Group Diabetes Register, secondary independent ascertainment from the National Diabetes Register. RESULTS: There were 202 incident cases of type 2 diabetes (96 boys, 48%). The mean age at diagnosis (±SD) was 14.6 ± 2.5 yr; 93% were overweight (International Obesity Taskforce Grade ≥1). Mean HbA1c was 8.8 ± 2.8%. Ethnicity was Caucasian 31%, Indigenous Australian 20%, Southeast Asian 11%, North African/Middle Eastern 9%, and NewZealander/Melanesian/Polynesian 8%. The mean annual incidence of type 2 diabetes was 3.0 per 100 000 per year (95% confidence interval (CI): 2.6-3.4) and did not change over time. The mean annual incidence of type 1 diabetes was 22.0 per 100 000 per year (95% CI: 20.8-23.1), and increased by 3.8% per year [incidence rate ratio IRR: 1.04, 95% CI: 1.02-1.06, p = 0.001]. Incidence was higher in Indigenous vs. non-Indigenous youth, IRR: 6.9 (95% CI: 4.7-10.2, p < 0.001). CONCLUSION: In 10-18 yr old youth, in Australia, the incidence of type 2 diabetes has remained steady during the last decade; however, the incidence of type 1 diabetes continues to rise. Most common diabetes in Australian youth is type 1 diabetes.

Improved insulin sensitivity and body composition, irrespective of macronutrient intake, after a 12 month intervention in adolescents with pre-diabetes; RESIST a randomised control trial.

BACKGROUND: A higher protein to carbohydrate ratio in the diet may potentiate weight loss, improve body composition and cardiometabolic risk, including glucose homeostasis in adults. The aim of this randomised control trial was to determine the efficacy of two structured lifestyle interventions, differing in dietary macronutrient content, on insulin sensitivity and body composition in adolescents. We hypothesised that a moderate-carbohydrate (40-45% of energy), increased-protein (25-30%) diet would be more effective than a high-carbohydrate diet (55-60%), moderate-protein (15%) diet in improving outcomes in obese, insulin resistant adolescents. METHODS: Obese 10-17 year olds with either pre-diabetes and/or clinical features of insulin resistance were recruited at two hospitals in Sydney, Australia. At baseline adolescents were prescribed metformin and randomised to one of two energy restricted diets. The intervention included regular contact with the dietician and a supervised physical activity program. Outcomes included insulin sensitivity index measured by an oral glucose tolerance test and body composition measured by dual-energy x-ray absorptiometry at 12 months. RESULTS: Of the 111 adolescents recruited, 85 (77%) completed the intervention. BMI expressed as a percentage of the 95th percentile decreased by 6.8% [95% CI: -8.8 to -4.9], ISI increased by 0.2 [95% CI: 0.06 to 0.39] and percent body fat decreased by 2.4% [95% CI: -3.4 to -1.3]. There were no significant differences in outcomes between diet groups at any time. CONCLUSION: When treated with metformin and an exercise program, a structured, reduced energy diet, which is either high-carbohydrate or moderate-carbohydrate with increased-protein, can achieve clinically significant improvements in obese adolescents at risk of type 2 diabetes. TRIAL REGISTRATION: Australian New Zealand Clinical Trail Registry ACTRN12608000416392 . Registered 25 August 2008.

Bone mineral content and density in Rett syndrome and their contributing factors.

This study used densitometry to investigate the areal bone mineral density (aBMD) and bone mineral content (BMC) in an Australian Rett syndrome cohort and to assess how factors such as genotype, epilepsy, BMI, and mobility affect these parameters. The influence of lean tissue mass (LTM) and bone area (BA) on total body BMC (TBBMC) was also investigated. Participants, recruited from the Australian Rett Syndrome Database (ARSD), had TBBMC and lumbar spine (LS) and femoral neck (FN) aBMD measured using Dual energy x-ray absorptiometry. Mean height standardized Z scores and CIs for the bone outcomes were obtained from multiple regression models. The mean height Z score for the FN aBMD was low at -2.20, while the LS aBMD was -0.72. The TBBMC mean height Z score was -0.62, although once adjusted for BA and LTM, the mean was above zero, suggesting that low BMC can be explained by narrow bones and decreased muscle mass, likely secondary to decreased mobility. Multiple linear regression identified the p.R168× and p.T158M mutations as the strongest predictors of low aBMC and BMD for all bone outcomes. The strong relationship between genotype, BMC, and aBMD is likely underpinned by the strong relationship between LTM, mobility, and bone outcome measures.

Persistently autoantibody negative (PAN) type 1 diabetes mellitus in children.

BACKGROUND: Autoantibody-negative children diagnosed with type 1 diabetes might have unrecognized monogenic or type 2 diabetes. RESEARCH DESIGN AND METHODS: At diagnosis of type 1 diabetes (between ages 0.5 and 16.3 yr, n = 470), autoantibodies [glutamic acid decarboxylase (GAD), insulinoma-associated protein 2 (IA2), insulin autoantibodies (IAA), and/or islet cell antibody (ICA)] were positive (ab+) in 330 and negative in 37 (unknown in 103). Autoantibody-negative patients were retested at median diabetes duration of 3.2 yr (range 0.9-16.2) for autoantibodies (GAD, IA2, ZnT8), human leukocyte antigen (HLA) typing, non-fasting C-peptide, and sequencing of HNF4A, HNF1A, KCNJ11, and INS. RESULTS: Nineteen (5% of 367) remained persistently autoantibody negative (PAN), 17 were positive on repeat testing (PORT), and 1 refused retesting. No mutations were found in PORT. One PAN was heterozygous for P112L mutation in HNF1A and transferred from insulin to oral gliclazide. Another PAN transferred to metformin and the diagnosis was revised to type 2 diabetes. The remaining 17 PAN were indistinguishable from the ab+ group by clinical characteristics. HLA genotype was at high risk for type 1 diabetes in 82% of remaining PAN and 100% of PORT. After excluding patients with diabetes duration <1 yr, C-peptide was detectable more frequently in the remaining PAN (7/16) and PORT (6/17) than in a random selection of ab+ (3/28, p = 0.03). CONCLUSIONS: The diagnosis of type 1 diabetes should be reevaluated in PAN patients, because a subset has monogenic or type 2 diabetes. The remaining PAN have relatively preserved C-peptide compared with ab+, suggesting slower ß-cell destruction, but a very high frequency of diabetogenic HLA, implying that type 1B (idiopathic) diabetes is rare.

Vitamin D deficiency in children with inflammatory bowel disease.

BACKGROUND: Osteopenia and osteoporosis are commonly seen in inflammatory bowel disease (IBD). Vitamin D deficiency potentially contributes to diminished bone acquisition in childhood. OBJECTIVES: The objectives of this study were to assess vitamin D in a group of Australian children with IBD and to ascertain associations between vitamin D status and key clinical factors, for example disease location and severity. METHODS: Data were obtained retrospectively from the records of children with IBD who had at least one measurement of serum 25-hydroxyvitamin D (25(OH)D) over a two-year period. Demographic variables, disease activity, inflammatory markers, disease location, duration, and therapy were recorded. Moderate and severe deficiency were defined as 25(OH)D <51 nmol/l and <30 nmol/l, respectively. Insufficiency was defined as 25(OH)D between 51 and 75 nmol/l. RESULTS: Overall, the mean 25(OH)D level in 78 children (104 measurements) was 71.2 (SD ± 26.5) nmol/l. Fifteen (19%) children were vitamin D deficient and 30 (38%) children were insufficient. Levels of 25(OH)D were not associated with disease location or use of immunosuppressive drugs. Children with vitamin D deficiency had greater corticosteroid exposure than those with normal status (P = 0.001). The mean 25(OH)D of 38 children treated with nutritional therapy at diagnosis was higher than for 17 children initially treated with corticosteroids (P = 0.04). CONCLUSIONS: A high proportion of these Australian children with IBD were vitamin D deficient. This emphasizes the importance of monitoring vitamin D status, and treating deficiency, in the management of pediatric IBD. The possible benefit of nutritional therapy in protection against vitamin D deficiency requires further prospective study.

Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers - RESIST. A randomised control trial investigating the effects of two different diets on insulin sensitivity in young people with insulin resistance and/or pre-diabetes.

BACKGROUND: Concomitant with the rise in childhood obesity there has been a significant increase in the number of adolescents with clinical features of insulin resistance and prediabetes. Clinical insulin resistance and prediabetes are likely to progress to type 2 diabetes and early atherosclerosis if not targeted for early intervention. There are no efficacy trials of lifestyle intervention in this group to inform clinical practice. The primary aim of this randomised control trial (RCT) is to determine the efficacy and effectiveness of two different structured lifestyle interventions differing in diet composition on insulin sensitivity, in adolescents with clinical insulin resistance and/or prediabetes treated with metformin. METHODS/DESIGN: This study protocol describes the design of an ongoing RCT. We are recruiting 108 (54 each treatment arm) 10 to 17 year olds with clinical features of insulin resistance and/or prediabetes, through physician referral, into a multi-centred RCT. All participants are prescribed metformin and participate in a diet and exercise program. The lifestyle program is the same for all participants except for diet composition. The diets are a high carbohydrate, low fat diet and a moderate carbohydrate, increased protein diet.The program commences with an intensive 3 month dietary intervention, implemented by trained dietitians, followed by a 3 month intensive gym and home based exercise program, supervised by certified physical trainers. To measure the longer term effectiveness, after the intensive intervention trial participants are managed by either their usual physician or study physician and followed up by the study dietitians for an additional 6 months. The primary outcome measure, change in insulin sensitivity, is measured at 3, 6 and 12 months. DISCUSSION: Clinical insulin resistance and prediabetes in the paediatric population are rapidly emerging clinical problems with serious health outcomes. With appropriate management these conditions are potentially reversible or at least their progression can be delayed. This research study is the first trial designed to provide much needed data on the effective dietary management for this cohort. This study will inform clinical practice guidelines for adolescents with clinical insulin resistance and may assist in preventing metabolic complications, type 2 diabetes and early cardiovascular disease. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registration Number ACTRN12608000416392.

Dietary intakes of children with Crohn's disease.

Approximately 25 % of individuals with Crohn's disease (CD), a life-long relapsing-remitting disease, are diagnosed during childhood and adolescence. Symptoms of CD, including abdominal pain, nausea and diarrhoea, can lead to reduced food intake, which may negatively have an impact on nutritional status during this critical period of growth and development. The aims of the present study were to assess the growth and adequacy of dietary intakes of children with CD at Sydney Children's Hospital, Randwick, and compare with healthy controls. Sixty-three subjects aged 10-16 years were recruited, including: children with active CD (n 18), children with CD in remission (n 23) and healthy controls (n 22). Dietary intake was assessed using a FFQ and compared with current Australian recommended dietary intakes (RDI). Growth and dietary intakes were compared between groups. Subjects with active CD had lower weight and BMI Z scores than children in remission and controls. The energy intakes of children with active CD and those in remission were significantly lower than estimated energy requirements (P = 0.001 and P = 0.03 respectively). Children with active CD did not meet the RDI for Fe and their Ca intake was lower than the RDI (P = 0.04). In conclusion, the dietary intake of children with active CD was impaired, with inadequate intakes of energy, Ca and Fe. Reduced energy intakes during active disease may contribute to poor weight gain and impaired growth. Quantifying nutrient intake and ascertaining requirements for nutritional supplementation are essential components of successful management in paediatric CD.

Insulin allergy desensitization with simultaneous intravenous insulin and continuous subcutaneous insulin infusion.

Persistent 'IgE-mediated' insulin allergy (type 1 allergy) (1), unresponsive to changes in insulin type or the use of antihistamines, necessitates desensitization. A number of case reports (2-7) and recent reviews (8, 9) have demonstrated that desensitization can be achieved with continuous subcutaneous insulin infusion (CSII), but in type 1 diabetes mellitus, the need to slowly increase insulin dose from sub-therapeutic levels competes with the need for glycaemic control and suppression of ketogenesis. Tolerance to intravenous (IV) insulin despite persistent life-threatening allergic reactions to subcutaneous human insulin (bolus or CSII) has been recently described (10). We present the cases of two unrelated 9-yr-old boys with persistent generalized urticarial reactions to subcutaneous injections of all available insulin types, despite treatment with oral antihistamines. After failed rapid desensitization to insulin delivered by either subcutaneous injection or CSII, the concurrent use of IV insulin allowed desensitization to CSII over 5-6 d.

Diagnosis and management of childhood obesity: a survey of general practitioners in South West Sydney.

AIM: To describe general practitioners' (GPs) diagnosis and management of overweight and obesity in children, their attitudes regarding obesity and their awareness of National Health and Medical Research Council (NHMRC) clinical practice guidelines. METHOD: A cross-sectional written survey of members of the Liverpool Division of General Practice (located in South West Sydney, Australia). RESULTS: Of 137 questionnaires sent, 85 (62%) were returned. Although the majority prescribed the correct interventions, there was variability in complications screening, ranging from 75% screening for psychosocial problems to 30% for fatty liver. Less than a third (28%) of GPs used NHMRC guidelines in their practice and only 9% used body mass index charts to correctly diagnose childhood obesity. GPs felt that childhood obesity was a significant issue and identified parental denial and lack of community support as barriers to treatment. CONCLUSION: Although NHMRC guideline adherence was far from universal, the GPs in our survey are motivated and aware of the importance of managing childhood obesity. If the primary care approach is to work, then GPs need support and education in an environment where there is greater community awareness of the impact of childhood obesity.

Fracture in Duchenne Muscular Dystrophy: Natural History and Vitamin D Deficiency.

The present study examined the natural history of fracture and vitamin D levels in Duchenne muscular dystrophy patients, who are vulnerable to osteoporosis and fractures. Retrospective analysis of a cohort of 48 Duchenne muscular dystrophy patients revealed that 43% of patients experienced ≥1 fracture. Fracture probabilities at ages 6, 9, 12, and 15 years were 4%, 9%, 31%, and 60% respectively, accelerating around the time of ambulation loss (mean age 11.8 ± 2.7 years). Chronic corticosteroid therapy was utilized in 69% of patients and was associated with all vertebral fractures. A history of vitamin D deficiency occurred in 84%, and 35% were currently deficient. Despite chronic vitamin D supplementation, 38% remained deficient. These results demonstrate that osteoporosis and fracture remain major concerns in Duchenne muscular dystrophy. Bone health should be optimized well before loss of ambulation, however current levels of vitamin D supplementation may be inadequate given high levels of deficiency.

Clinical Guidelines for Management of Bone Health in Rett Syndrome Based on Expert Consensus and Available Evidence.

OBJECTIVES: We developed clinical guidelines for the management of bone health in Rett syndrome through evidence review and the consensus of an expert panel of clinicians. METHODS: An initial guidelines draft was created which included statements based upon literature review and 11 open-ended questions where literature was lacking. The international expert panel reviewed the draft online using a 2-stage Delphi process to reach consensus agreement. Items describe the clinical assessment of bone health, bone mineral density assessment and technique, and pharmacological and non-pharmacological interventions. RESULTS: Agreement was reached on 39 statements which were formulated from 41 statements and 11 questions. When assessing bone health in Rett syndrome a comprehensive assessment of fracture history, mutation type, prescribed medication, pubertal development, mobility level, dietary intake and biochemical bone markers is recommended. A baseline densitometry assessment should be performed with accommodations made for size, with the frequency of surveillance determined according to individual risk. Lateral spine x-rays are also suggested. Increasing physical activity and initiating calcium and vitamin D supplementation when low are the first approaches to optimizing bone health in Rett syndrome. If individuals with Rett syndrome meet the ISCD criterion for osteoporosis in children, the use of bisphosphonates is recommended. CONCLUSION: A clinically significant history of fracture in combination with low bone densitometry findings is necessary for a diagnosis of osteoporosis. These evidence and consensus-based guidelines have the potential to improve bone health in those with Rett syndrome, reduce the frequency of fractures, and stimulate further research that aims to ameliorate the impacts of this serious comorbidity.

Longitudinal bone mineral content and density in Rett syndrome and their contributing factors.

Bone mass and density are low in females with Rett syndrome. This study used Dual energy x-ray absorptiometry to measure annual changes in z-scores for areal bone mineral density (aBMD) and bone mineral content (BMC) in the lumbar spine and total body in an Australian Rett syndrome cohort at baseline and then after three to four years. Bone mineral apparent density (BMAD) was calculated in the lumbar spine. Annual changes in lean tissue mass (LTM) and bone area (BA) were also assessed. The effects of age, genotype, mobility, menstrual status and epilepsy diagnosis on these parameters were also investigated. The baseline sample included 97 individuals who were representative of the total live Australian Rett syndrome population under 30years in 2005 (n=274). Of these 74 had a follow-up scan. Less than a quarter of females were able to walk on their own at follow-up. Bone area and LTM z-scores declined over the time between the baseline and follow-up scans. Mean height-standardised z-scores for the bone outcomes were obtained from multiple regression models. The lumbar spine showed a positive mean annual BMAD z-score change (0.08) and a marginal decrease in aBMD (-0.04). The mean z-score change per annum for those 'who could walk unaided' was more positive for LS BMAD (p=0.040). Total body BMD mean annual z-score change from baseline to follow-up was negative (-0.03). However this change was positive in those who had achieved menses prior to the study (0.03, p=0,040). Total body BMC showed the most negative change (-0.60), representing a decrease in bone mineral content over time. This normalised to a z-score change of 0.21 once adjusted for the reduced lean tissue mass mean z-score change (-0.21) and bone area mean z-score change (-0.14). Overall, the bone mineral content, bone mineral density, bone area and lean tissue mass z-scores for all outcome measures declined, with the TB BMC showing significant decreases. Weight, height and muscle mass appear to have impacts on bone formation and we recommend that nutritional intake should be closely monitored and a physical activity plan developed to optimise bone health. Pubertal progression should also be assessed in conjunction with serial densitometry assessments to track bone mass and density changes over time.

Mid-femur geometry and biomechanical properties in 15- to 18-yr-old female athletes.

PURPOSE: Right-leg mid-femur geometry and biomechanical indices of bone strength were compared among elite cyclists (CYC), runners (RUN), swimmers (SWIM), triathletes (TRI), and controls (C)-10 subjects per group. METHODS: Bone cross-sectional areas (CSA), volumes (Vol), and cross-sectional moments of inertia (CSMI) were assessed by magnetic resonance imaging (MRI), and cortical volumetric bone density (volBMD) was determined as the quotient of DXA-derived bone mineral content (BMC) and MRI-derived cortical bone volume. Bone strength index (BSI) was calculated as the product of cortical volBMD and CSMI. RESULTS: RUN had higher (P < 0.05) size- (femur length and body mass) adjusted (ANCOVA) cortical CSA than C, SWIM, and CYC; and higher size, age, and years of sport-specific training- (YST) adjusted cortical CSA than SWIM and CYC. TRI had higher (P < 0.05) size-adjusted CSA than SWIM. SWIM and CYC had significantly larger (P < 0.05) size-adjusted medullary cavity CSA than RUN and TRI, and the difference between CYC and RUN persisted after additional adjustment for age and YST. RUN had significantly (P < 0.05) greater size-adjusted CSMI and BSI than C, SWIM, and CYC; and higher size, age, and YST-adjusted CSMI and BSI than SWIM and CYC. Mid-femur areal bone mineral density (BMD) was significantly (P < 0.05) higher for RUN compared with CYC only, but there were no other differences among groups for BMC, bone volumes, or volumetric total or cortical BMD. CONCLUSIONS: Running, a weight-bearing exercise, is associated with more favorable geometric and biomechanical characteristics in relation to bone strength, compared with the weight supported activities of swimming and cycling. Differences may reflect skeletal adaptations to the specific mechanical-loading patterns inherent in these sports.