Wolfgang Hogler

Importance of lean mass in the interpretation of total body densitometry in children and adolescents

OBJECTIVEnMost studies that use total body dual energy x-ray absorptiometry (DEXA) in children rely on areal bone mineral density (BMD=bone mineral content [BMC]/bone area [BA]) and compare the output with age- and sex-specific normative data. Because this approach is prone to size-related misinterpretation, this study focuses on the interrelations among BMC, body size (height), and lean tissue mass (LTM).nnnSTUDY DESIGNnThis cross-sectional study presents normative total body LTM data in relation to height and BMC for 459 healthy white subjects (249 female), 3 to 30 years of age. Guidelines for DEXA interpretation in children are provided and illustrated for patients with growth hormone deficiency (n=5) and anorexia nervosa (n=5).nnnRESULTSnLTM/height tended to be greater in male than in girls. The BMC/LTM ratio was greater in female than in boys (P<.001), even after adjustment for age and height. Sex-specific reference curves were created for LTM/height, the BMC/LTM ratio, BA/height, and BMC/BA.nnnCONCLUSIONSnWe recommend that total body DEXA in children should be interpreted in 4 steps: (1) BMD or BMC/age, (2) height/age, (3) LTM/height, and (4) BMC/LTM ratio for height. This allows differentiation of the origin of a low BMD or BMC/age, for example, short stature and primary, secondary, and mixed bone defects.

The re-emerging burden of rickets: a decade of experience from Sydney

Aim: To define the demographics and clinical characteristics of cases presenting with nutritional rickets to paediatric centres in Sydney, Australia. Methods: Retrospective descriptive study of 126 cases seen from 1993 to 2003 with a diagnosis of vitamin D deficiency and/or confirmed rickets defined by long bone x ray changes. Results: A steady increase was seen in the number of cases per year, with a doubling of cases from 2002 to 2003. Median age of presentation was 15.1 months, with 25% presenting at less than 6 months of age. The most common presenting features were hypocalcaemic seizures (33%) and bowed legs (22%). Males presented at a younger age, with a lower weight SDS, and more often with seizures. The caseload was almost exclusively from recently immigrated children or first generation offspring of immigrant parents, with the region of origin predominantly the Indian subcontinent (37%), Africa (33%), and the Middle East (11%). Seventy nine per cent of the cases were born in Australia. Eleven cases (all aged <7 months) presented atypically with hyperphosphataemia. Conclusions: This large case series shows that a significant and increasing caseload of vitamin D deficiency remains, even in a developed country with high sunlight hours. Cases mirror recent immigration trends. Since birth or residence in Australia does not appear to be protective, screening of at risk immigrant families should be implemented through public health policies.

A comparison of bone geometry and cortical density at the mid-femur between prepuberty and young adulthood using magnetic resonance imaging

In upper extremity bones, a sexual dimorphism exists in the development of periosteal and endocortical bone surfaces during growth. Little is known about developmental patterns of bone geometry at weight-bearing bones like the femur. Using MRI and dual energy X-ray absorptiometry (DXA), this study assessed the differences in mid-femoral total (TA), cortical (CA) and medullary areas (MA), cortical thickness, and cortical density (BMD(compartment)) between prepuberty and young adulthood in 145 healthy subjects (94 females) 6 to 25 years old. Additionally, agreement between mid-femoral total bone volume (TV) measurements by DXA and MRI were investigated. In both sexes, TA, CA, MA, and cortical thickness were significantly larger in adults compared to prepubertal subjects (P < 0.001), and males had greater values than females. This sex difference persisted for TA, CA, and cortical thickness (P < 0.05), but not MA, after adjusting for femur length and weight. Mean (SD) cortical BMD increased from 1.05 (0.07) and 1.09 (0.10) g/cm(3) in prepubertal children to 1.46 (0.14) and 1.42 (0.1) g/cm(3) in young adults, females and males, respectively (P < 0.001). TV measurements by DXA were significantly greater than by MRI (P < 0.001) in young adults. In conclusion, periosteal and endocortical expansion and increasing cortical BMD are the growth processes found at the mid-femur in both sexes. Our findings contrast to that in upper extremity bones, where MA is constant in females during growth. The difference in femoral bone development may be due to higher strains caused by weight bearing and genetic factors. DXA, in contrast to MRI, is inaccurate in the determination of mid-femoral TV measures.

Sex-specific developmental changes in muscle size and bone geometry at the femoral shaft

INTRODUCTIONnWhen expressed as a percentage of the average result in young adults, bone mineral content lags behind bone length before puberty. Even though this observation has led to speculation about bone fragility in children, such relationships could simply be due to scaling effects when measures with different geometrical dimensions are compared.nnnMETHODSnThe study population comprised 145 healthy subjects (6-25 years, 94 females). Magnetic resonance imaging and dual-energy X-ray absorptiometry were used to determine femur length, bone mineral content, cortical bone mineral density, cross-sectional bone geometry (bone diameter; cortical thickness; total, cortical and medullary areas; cross-sectional and polar moments of area; bone strength index) and muscle area at the proximal one-third site of the femur. Results were dimensionally scaled by raising two-, three- and four-dimensional variables to the power of 1/2, 1/3 and 1/4, respectively. Sex-differences were also assessed before and after functionally adjusting variables for femur length and weight or muscle size.nnnRESULTSnIn prepubertal children, unscaled results expressed as percentages of adult values were lowest for variables with the highest dimensions (e.g., moments of area<bone mineral content<cross-sectional areas<femur length). However, when dimensionally scaled, results in children represented similar percentages of the respective average adult values, even after functional adjustments. Before puberty, there was no sex-difference in adjusted bone or muscle variables. After puberty, males had greater total and cortical bone area, bone diameter, moments of area, bone strength index and muscle area than women, both in absolute terms as well as adjusted for femur length and weight. The largest sex-difference was found for muscle area. When compared relative to muscle size, young adult women attained greater total and cortical bone area than men.nnnCONCLUSIONSnGrowth in femoral length, diameter, mass and strength appears well coordinated before puberty. Postpubertal females have narrower femora, less bone strength and muscle size than males. However, when muscle size is taken into account, females have a larger femoral bone cross-section and more cortical bone. These sex-differences likely result from a combination of mechanical and hormonal effects occurring during puberty.

Severe transient hyperinsulinaemic hypoglycaemia: two neonates without predisposing factors and a review of the literature

We report on transient hyperinsulinism (HI), presenting as severe congenital HI, in two neonates born without intrauterine growth restriction, maternal diabetes, perinatal asphyxia or Rhesus/platelet isoimmunisation. The neonates developed early (<6xa0h of life), symptomatic, non-ketotic hypoglycaemia (0–0.66xa0mmol/l), associated with elevated insulin levels (40–200xa0mU/l), and required high glucose infusion rates (22–24xa0mg/kg per min) to maintain normoglycaemia. However, both babies were diazoxide-sensitive and did not require glucose infusions beyond 2 weeks of life. Neither neonate had elevated serum ammonia levels or evidence of a metabolic disorder. Conclusion:transient hyperinsulinism can occur in newborns delivered uneventfully without significant perinatal complications. The unusual sensitivity to medical treatment in these cases of neonatal-onset hyperinsulinaemic hypoglycaemia underscores the importance of careful medical management of severe congenital hyperinsulinism. Careful consideration of the indication and if necessary, timing and extent of pancreatectomy is required, while maintaining euglycaemia to protect the developing brain.

Prolonged iron depletion after allogeneic 2-unit RBC apheresis.

BACKGROUND: Allogeneic 2‐unit RBC apheresis is a safe procedure offering many advantages for donors and blood banks. A controlled study was performed to determine whether the recommended minimum interval of 4 months between 2‐unit RBC apheresis donations is appropriate in terms of the recovery of RBCs and the regeneration of iron stores.

Comparison of the response to bisphosphonate treatment between acute lymphoblastic leukaemia and osteogenesis imperfecta type I

Genant et al, Verebral fracture assessment using a semiquantitative technique. LSBMAD improvement in ALL is comparable to that in children with type I OI. Symptomatic improvement and vertebral remodelling variable Osteoporosis in children with osteogenesis imperfecta type 1 (OI) and acute lymphoblastic Leukaemia (ALL) is characterised by high bone turnover. However the ability of spontaneous healing and reshaping of bone is retained in ALL even in the absence of bisphosphonate (BP) therapy, but impaired in OI. Background