Impairment of Bone Health in Pediatric Patients with Hemolytic Anemia

Introduction Sickle cell anemia and thalassemia result in impaired bone health in both adults and youths. Children with other types of chronic hemolytic anemia may also display impaired bone health. Study Design To assess bone health in pediatric patients with chronic hemolytic anemia, a cross-sectional study was conducted involving 45 patients with different forms of hemolytic anemia (i.e., 17 homozygous sickle cell disease and 14 hereditary spherocytosis patients). Biochemical, radiographic and anamnestic parameters of bone health were assessed. Results Vitamin D deficiency with 25 OH-vitamin D serum levels below 20 ng/ml was a common finding (80.5%) in this cohort. Bone pain was present in 31% of patients. Analysis of RANKL, osteoprotegerin (OPG) and osteocalcin levels indicated an alteration in bone modeling with significantly elevated RANKL/OPG ratios (control: 0.08+0.07; patients: 0.26+0.2, P = 0.0007). Osteocalcin levels were found to be lower in patients compared with healthy controls (68.5+39.0 ng/ml vs. 118.0+36.6 ng/ml, P = 0.0001). Multiple stepwise regression analysis revealed a significant (P<0.025) influence of LDH (partial r2 = 0.29), diagnosis of hemolytic anemia (partial r2 = 0.05) and age (partial r2 = 0.03) on osteocalcin levels. Patients with homozygous sickle cell anemia were more frequently and more severely affected by impaired bone health than patients with hereditary spherocytosis. Conclusion Bone health is impaired in pediatric patients with hemolytic anemia. In addition to endocrine alterations, an imbalance in the RANKL/OPG system and low levels of osteocalcin may contribute to this impairment

Prevalence of osteopathologies in a single center cohort of survivors of childhood primary brain tumor

BackgroundChildhood primary brain tumors (CPBT) are the second largest group of childhood malignancies and associated with a high risk for endocrine late effects.ObjectiveTo assess endocrine late effects and their relevance for the development of osteopathologies in survivors.MethodsThis single center cross sectional study investigated data from 102 CPBT survivors with a mean age of 13.0 years and a mean age at diagnosis of 8.7 years. Clinical, biochemical, radiographic, and anamnestic data regarding endocrine and bone health were obtained at study visits. In addition, data regarding tumor stage and therapy was obtained by chart review. An expert opinion was applied to define presence of osteopathologies.ResultsImpaired bone health, defined by at least one pathological screening parameter, was present in 65% of patients. 27.5% were found to have overt osteopathologies per expert opinion. 37.8% displayed a severe vitamin D deficiency (25-OH vitamin D &lt; 10 ng/ml) and 11% a secondary hyperparathyroidism. Patients with osteopathologies had lower 25-OH vitamin D levels compared to patients without osteopathologies. Multiple endocrine late effects were present: diabetes insipidus in 10.8%, aberrant pubertal development in 13.7%, central hypocortisolism in 14.9%, thyroid dysfunction in 23.8% and growth hormone deficiency in 21.8%. A total of 31.3% of survivors displayed any endocrinopathy. Tumors located near hypothalamic structures and patients who received irradiation had a higher likelihood of endocrine morbidity.ConclusionThis study indicates that endocrine deficiencies are common in pediatric survivors of CPBTs. Osteopathologies are present in this cohort. A prominent effect of hormonal deficiencies on bone health was not detected, possibly because patients were sufficiently treate for their endocrine conditions or indicating resilience of the childhood bone remodeling process. Vitamin D deficiency is frequent and should be treated as recommended

Maternal vitamin D status in preeclampsia: seasonal changes are not influenced by placental gene expression of vitamin D metabolizing enzymes.

Preeclampsia, a hypertensive disorder in pregnancy develops in 2-8% of pregnancies worldwide. Winter season and vitamin D deficiency have been associated with its onset.To investigate the influence of season on maternal vitamin D status and placental vitamin D metabolism.25-OH vitamin D and 1,25-(OH)2 vitamin D were measured in maternal serum obtained during the winter or summer months from 63 pregnant women at delivery (43 healthy, 20 preeclampsia). In a subgroup, mRNA expression of CYP24A1 (24-hydroxylase), CYP27B1 (1α-hydroxylase) and VDR (vitamin D receptor) were quantified by real time PCR in placental samples of 14 women with normal pregnancies and 13 with preeclampsia.In patients with preeclampsia,25-OH vitamin D levels were lower, but differed significantly from controls only in summer (18.21±17.1 vs 49.2±29.2 ng/mL, P<0.001), whereas 1,25-(OH)2 vitamin D levels were significantly lower only in winter (291±217 vs 612.3±455 pmol/mL, P<0.05). A two-factorial analysis of variance produced a statistically significant model (P<0.0001) with an effect of season (P<0.01) and preeclampsia (P = 0.01) on maternal 25-OH vitamin D levels, as well as a significant interaction between the two variables (P = 0.02). Placental gene expression of CYP24A1, CYP27B1, and VDR did not differ between groups or seasons. A negative correlation between placental gene expression of CYP24A1 and CYP27B1 was observed only in healthy controls (r = -0.81, P<0.0001).Patients with preeclampsia displayed lower vitamin D serum levels in response to seasonal changes.The regulation of placental CYP24A1, but not of the VDR or CYP27B1 might be altered in preeclampsia

Cardiorespiratory fitness in adolescents and young adults with Klinefelter syndrome – a pilot study

Background Klinefelter syndrome (KS) may be associated with a wide spectrum of phenotypic changes including endocrine, metabolic, cognitive, psychiatric and cardiorespiratory pathologies in adults. However, in adolescence the clinical phenotype of KS is not well described, especially regarding physical fitness. The present study reports on cardiorespiratory function in adolescents and young adults with KS. Methods Adolescents and young adults with KS were recruited in a cross-sectional pilot study. Biochemical parameters of fitness including hormonal status, a body impedance analysis, the grip strength, the amount of physical activity at home for 5 days via trackbands and anamnestic parameters were assessed. In addition, participants underwent an incremental symptom-limited cardiopulmonary exercise test (CPET) on a bicycle ergometer. Results Nineteen participants with KS aged 15.90 ± 4.12 years (range: 9.00 - 25.00) participated in the study. Pubertal status was Tanner 1 (n = 2), Tanner 2 - 4 (n = 7) and Tanner 5 (n = 10). Seven participants received testosterone replacement therapy. Mean BMI z-score was 0.45 ± 1.36 and mean fat mass was 22.93% ± 9.09. Grip strength was age-appropriate or above normal. 18 participants underwent CPET with subnormal results for maximum heart rate (z-score -2.84 ± 2.04); maximum workload (Watt max ; z score -1.28 ± 1.15) and maximum oxygen uptake per minute (z- score -2.25 ± 2.46). Eight participants (42.1%) met the criteria for chronotropic insufficiency (CI). Data from track-bands showed sedentary behavior for 81.15% ± 6.72 of the wear time. Conclusion A substantial impairment of cardiopulmonary function can be detected in this group of boys to young adults with KS, including chronotropic insufficiency in 40%. The track-band data suggest a predominantly sedentary lifestyle, despite normal muscular strength as assessed via grip strength. Future studies need to investigate the cardiorespiratory system and its adaption to physical stress in a larger cohort and in more detail. It is feasible that the observed impairments contribute to the avoidance of sports in individuals with KS and may contribute to the development of obesity and the unfavorable metabolic phenotype

mRNA expression of placental CYP24A1, CYP27B1 and VDR (mean ± SD and (range) do not differ between patients with preeclampsia and healthy controls.

<p>mRNA expression of placental CYP24A1, CYP27B1 and VDR (mean ± SD and (range) do not differ between patients with preeclampsia and healthy controls.</p

Boxplots showing the smallest observation (lower bar), lower and upper quartile (box), median (line in the box) and largest observation (upper bar) of a) maternal 25-OH vitamin D serum levels (ng/mL) in winter (grey box) and summer (open box).

<p>Maternal 25-OH vitamin D levels differ between patients with preeclampsia and healthy controls in the summer (** p<0.01). b) Maternal 1,25-(OH)₂ vitamin D (pmol/mL) serum levels are similar in both groups, but significantly lower during winter months in patients with preeclampsia (** p<0.01).</p

Correlation of placental mRNA expression of CYP24A1 (x-axis) and a) CYP27B1 or b) maternal 25-OH vitamin D (ng/ml) in healthy controls (black circles) and patients with preeclampsia (transparent circles).

<p>a) Placental gene expression of CYP24A1 correlates negatively with CYP27B1 expression in healthy controls (r = −0.81, <i>P</i><0.0001, solid line) but not in the patients with preeclampsia (dotted line). b) CYP24A1 correlates negatively with maternal 25-OH vitamin D levels (r = −0.76, <i>P</i> = 0.01) in patients with preeclampsia (dotted line).</p

Patient characteristics (mean + SD and (range)) for age, pre-pregnancy BMI, maternal calcium, 25- OH vitamin D, 1,25-(OH)₂ vitamin D levels in serum, systolic (SBP) and diastolic (DBP) blood pressure on admission to the hospital, as well as child length, weight, and BMI standard deviation scores (SDS) at birth.

<p>In patients with preeclampsia, maternal 25-OH vitamin D levels are significantly lower than in healthy controls. * differs from healthy controls (*<i>P</i><0.05, ** <i>P</i><0.01) ^#blood pressure obtained on admission to hospital was below the criterion for preeclampsia in one patient, despite preeclampsia with proteinuria and elevated blood pressure readings before and after admission.</p

mRNA expression of placental CYP24A1, CYP27B1 and VDR (mean ± SD and (range) do not differ between patients with preeclampsia and healthy controls.

<p>mRNA expression of placental CYP24A1, CYP27B1 and VDR (mean ± SD and (range) do not differ between patients with preeclampsia and healthy controls.</p

Pediatric Survivors of Retinoblastoma Are at Risk for Altered Bone Metabolism After Chemotherapy Treatment Early in Life

<div><p>Survivors of childhood cancer frequently suffer from endocrine late effects, which are, at least partly, attributed to toxic effects of chemotherapy. Treatment of retinoblastoma typically involves chemotherapy at a very young age. The authors conducted a cross-sectional study to assess bone health in a pediatric cohort of 33 survivors of retinoblastoma (mean age: 4.4 years) who had undergone chemotherapy treatment at an especially young age (mean age: 0.76 years). Of these patients, 14 had unilateral and 19 bilateral retinoblastoma. Polychemotherapy consisted of treatment with cyclophosphamide, etoposide, vincristine, and carboplatin. Ten patients had undergone external beam radiotherapy. Clinical and biochemical parameters of growth, pubertal development, and bone health were obtained. A vitamin D deficiency was found in 51.7% of the patients, and 13.7% of patients displayed severe vitamin D deficiency. Secondary hyperparathyroidism and altered readings for bone formation or resorption markers were present in 15%. Nine percent reported bone pain or experienced fractures of the long bones after primary diagnosis. No difference between children with bilateral and unilateral disease or irradiated versus nonirradiated children was observed. The parameters of thyroid function, growth, and pubertal development were within age-appropriate norms in almost all children. In conclusion, altered parameters of bone health can be present in survivors of retinoblastoma at a young age and warrant regular follow-up in these children. The endocrine hypothalamic-pituitary axes, however, were not impaired at this early age in this group of survivors of retinoblastoma.</p></div