Pisit Pitukcheewanont

Increased Body Weight and Decreased Radial Cross‐Sectional Dimensions in Girls with Forearm Fractures

A large number of children sustain fractures after relatively minor trauma and several investigators have associated these fractures to a deficient accumulation of bone during growth. This study was conducted to better characterize the skeletal phenotype associated with low‐energy impact fractures of the forearm in girls. The densities of cancellous, cortical, and integral bone and the cross‐sectional area were measured in the radius of 100 healthy white girls (aged 4‐15 years) using computed tomography (CT); 50 girls had never fractured and 50 girls had sustained a forearm fracture within the previous month. Fractured and nonfractured groups were matched for age, height, weight, and Tanner stage of sexual development. Compared with controls, girls with fractures had, on average, 8% smaller cross‐sectional area at the distal radius (1.82 ± 0.50 cm2 vs. 1.97 ± 0.42 cm2; p < 0.0001) but similar cancellous, integral, and cortical bone densities. Neither radial length nor the amount of fat or muscle at the midshaft of the radius differed between girls with and without fractures. Both study subjects and matched controls were overweight. Although mean height was at the 50th percentile, mean weight was at the 90th percentile for age‐adjusted normal values. Girls who sustain forearm fractures after minor trauma have small cross‐sectional dimensions of the radius and tend to be overweight. The smaller cross‐sectional area confers a biomechanical disadvantage that, coupled with the greater body weight, increases the vulnerability to fracture after a fall.

Biochemical Markers of Bone Turnover and the Volume and the Density of Bone in Children at Different Stages of Sexual Development

Bone mass and biochemical markers of bone turnover increase significantly during puberty. We studied the possible relationships between markers of bone formation and bone resorption and increases in skeletal size, bone volume, and bone density in healthy children at different stages of sexual development. Serum concentrations of bone specific alkaline phosphatase (BALP) and osteocalcin (bone Gla protein, BGP), urinary levels of pyridinoline (Pyr) and deoxypyridinoline (Dpyr) and computed tomography (CT) measurements of the cross‐sectional areas of the vertebrae and the femurs, the apparent density of cancellous bone in the vertebrae, and the volume and the material density of cortical bone in the femurs were determined in 126 boys and 143 girls, ages 7–18 years. Serum levels of BALP and BGP and urinary concentrations of Pyr and Dpyr peaked in early puberty and were lowest in the later stages of puberty. CT measurements for the cross‐sectional areas of the vertebrae and the femurs, the femoral cortical bone areas, and the apparent density of cancellous bone increased in all children during puberty, while values for material bone density did not change significantly with the stage of sexual development. BALP and BGP showed significant inverse correlations with the material density of bone (r = –0.23 and –0.24, respectively), but no association with bone volume in the appendicular or axial skeleton. In contrast, Pyr and Dpyr correlated with femoral cross‐sectional area (r = –0.24 and –0.33, respectively) and cortical bone area (r = –0.29 and –0.33, respectively), and with the apparent density of vertebral cancellous bone (r = –0.26 and –0.19, respectively), but not with the material density of bone. We conclude that, during puberty, there is a differential association between the two components of bone mass and the markers of bone formation and bone resorption; while markers of bone formation are related to the material density of bone, markers of bone resorption are related to the volume of bone.

Insulin pump therapy in Type 1 pediatric patients: now and into the year 2000

There are a number of medical conditions such as growth failure in children, pregnancy, lipid abnormalities, and early complications that are improved by the meticulous glycemic control that can be achieved with insulin pump therapy (CSII). By using an insulin pump, many patients with severe hypoglycemia, the dawn phenomenon, extremes of glycemic excursion, recurrent diabetic ketoacidosis (DKA) and hypoglycemia unawareness have amelioration of these problems. However, pump therapy involves problems such as weight gain, recurrent ketosis due to pump failure, infections, and risk of hypoglycemia.

Extended mutational analyses of FGFR1 in osteoglophonic dysplasia.

Emily G. Farrow, Siobhan I. Davis, Sean D. Mooney, Peter Beighton, Leo Mascarenhas, Yvonne R. Gutierrez, Pisit Pitukcheewanont, and Kenneth E. White* Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa Divisions of Hematology/Oncology, Children’s Hospital Los Angeles, Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, California General Pediatrics, Children’s Hospital Los Angeles, Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, California Center for Endocrinology, Diabetes and Metabolism, Children’s Hospital Los Angeles, Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, California

Gorham's disease and diffuse lymphangiomatosis in children and adolescents†

Gorhams disease is a rare disorder of unknown etiology and variable clinical presentation that is characterized by proliferation of thin‐walled vascular channels resulting in destruction and resorption of osseous matrix. The condition is frequently under recognized or misdiagnosed. There is no standard treatment defined for this disease. Here we report on eight children diagnosed with Gorhams disease at our institution over a ten‐year period. Soft tissue lymphangioma was present in seven and six children had splenic involvement. Disease stabilization and improvement was observed on treatment with interferon alpha‐2b and bisphosphonate therapy. Pediatr Blood Cancer 2011;56:667–670.

Characteristics of glycemic control in young children with type 1 diabetes.

Abtract: Background: The Diabetes Control and Complications Trial (DCCT) demonstrated that the rate‐limiting step to the intensification of diabetes management in adolescents and adults was hypoglycemia. Young children were presumed to be at even greater risk for hypoglycemia with severe consequences, particularly if they had HbA1c levels < 8%.

Enteral calcium infusion used successfully as treatment for a patient with hereditary vitamin D resistant rickets (HVDRR) without alopecia: a novel mutation.

BACKGROUND We report a novel mutation in a case of hereditary vitamin D resistant rickets (HVDRR) without alopecia and successful management of this condition with the intravenous formulation of calcium chloride delivered via gastric tube. CLINICAL CASE A 22 month old male (length -3.4 SDS; weight -2.1 SDS) presented with failure to thrive, short stature, severe hypocalcemia and gross motor delay. He did not have alopecia. Initial blood tests and history were thought possibly to suggest vitamin D deficiency rickets: calcium 5.1mg/dL, (8.8-10.8); phosphorus 4.1mg/dL, (4.5-5.5); alkaline phosphatase 1481 U/L (80-220); intact PTH 537.1 pg/mL (10-71). Subsequently, vitamin D studies returned that were consistent with HVDRR: 25-hydroxyvitamin D 34 ng/mL (20-100); 1,25-dihydroxyvitamin D 507 pg/mL. This diagnosis was confirmed by DNA sequencing. His subsequent clinical course was complicated by the fact that IV calcium was not a viable option for this patient, and his calcium levels could not be well controlled on oral calcium citrate or calcium glubionate therapy. Eventually, we were able to maintain calcium levels above 8 mg/dL using the intravenous preparation of calcium chloride administered via gastric tube. GENETIC STUDIES A unique homozygous T to C base substitution was found in exon 6 in the vitamin D receptor (VDR) gene. This mutation causes leucine to be converted to proline at position 227 in helix 3 in the VDR ligand binding domain (LBD). The mutation rendered the VDR non-functional, leading to HVDRR, with absence of alopecia. CONCLUSION HVDRR should be considered in a patient with profound hypocalcemia which is refractory to conventional therapy of vitamin D deficiency rickets even without evidence of alopecia. We report the first case of HVDRR with a novel mutation in the LBD that was successfully treated with enteral treatment using a calcium chloride infusion.

Quantitative Computed Tomography Measurements of Bone Mineral Density in Prepubertal Children with Congenital Hypothyroidism Treated with L-Thyroxine

Low bone density (BD) has been reported in patients with hyperthyroidism. Whether or not levothyroxine (LT4) therapy in children with congenital hypothyroidism (CH) affects BD is unclear. Medical records of 45 patients with various etiologies of CH who had at least one BD measurement (32 female, mean age 7.6 +/- 2.6 years) were reviewed. The mean LT4 dose was 3.6 +/- 0.88 microg/kg/day. Cancellous bone density (CaBD) was measured by quantitative computed tomography (CT) in all 45 patients and 20 had measurements of cortical bone density (CoBD), cross-sectional area (CSA) and cortical bone area (CBA) of the femur. TSH levels were considered partially or completely suppressed when values were <1.0 or <0.5 microIU/ml, respectively. The control group consisted of age- and gender-matched healthy children. No significant differences were found in CaBD, CoBD, CSA, or CBA between patients with CH and controls. There were no significant differences between initial and subsequent BD measurements. No correlations were found between CaBD and etiology of CH, dose or duration of LT4 therapy, or serum TSH. In pre-pubertal children with CH, LT4 appears to have no significant effect on BD. Moreover, absence or hypoplasia of the thyroid parenchyma appears to have no significant impact on bone formation within the first 10 years of life.

Effects of vitamin D repletion on glycemic control and inflammatory cytokines in adolescents with type 1 diabetes.

Little is known about the relationship between vitamin D deficiency and adolescents with type 1 diabetes. On the basis of adult studies showing that vitamin D improves insulin sensitivity and decreases inflammatory cytokines linked to microvascular complications, we hypothesized that treating vitamin D deficiency in adolescents with type 1 diabetes would improve glycemia and reduce inflammatory markers.

Bone size and density measurements in prepubertal children with Turner syndrome prior to growth hormone therapy

SummaryUsing computed tomography (CT), we found the decreases in bone size of vertebrae and femur, cortical bone area (CBA) of femur and bone density (BD) of vertebrae in prepubertal female with Turner syndrome (TS) compared to those of controls.IntroductionBone mineral density results from previous studies utilizing single-photon absorptiometry (SPA) or dual-energy X-ray absorptiometry (DXA) in children with TS are controversial. The present study used CT to assess the differences in cancellous and cortical bone size and BD between prepubertal TS patients prior to growth hormone therapy and historical age and ethnicity-matched female controls.MethodsAnthropometrics and CT bone measurements including cross-sectional area (CSA) and BD of lumbar vertebrae and femur and CBA of femur in prepubertal TS females were reviewed and compared with those in controls.ResultsTwenty-two prepubertal TS patients had delayed bone age, were shorter and lighter than controls (Ps < 0.001). After adjusting for weight, height and skeletal age, vertebral BD and CBA of the femur were lower in patients than in controls (P < 0.001 and P = 0.021, respectively). However, after additional adjusting for puberty, results were not different from controls. While a positive correlation between vertebral BD and age was noted in controls (r = 0.367, P = 0.092), a significant negative correlation was noted in patients (r = −0.615, P = 0.002).ConclusionsWhile the decrease in vertebrae and femur sizes of patients with TS appeared to be secondary to their small body size, the decreased BD of vertebrae and CBA of femur were likely secondary to estrogen deficiency.