To clarify the role of the intestine, kidney, and bone in maintaining calcium homeostasis during pregnancy and lactation and after the resumption of menses, a longitudinal comparison was undertaken of 14 well-nourished women consuming approximately 1200 mg Ca/d. Measurements were made before conception (prepregnancy), once during each trimester of pregnancy (T1, T2, and T3), early in lactation at 2 mo postpartum (EL), and 5 mo after resumption of menses. Intestinal calcium absorption was determined from the enrichment of the first 24-h urine sample collected after administration of stable calcium isotopes. Bone mineral of the total body and lumbar spine was measured by dual-energy X-ray absorptiometry and quantitative computerized tomography, respectively. Twenty-four-hour urine and fasting serum samples were analyzed for calcium, calcitropic hormones, and biochemical markers of bone turnover. Despite an increase in calcium intake during pregnancy, true percentage absorption of calcium increased from 32.9+/-9.1% at prepregnancy to 49.9+/-10.2% at T2 and 53.8+/-11.3% at T3 (P < 0.001). Urinary calcium increased from 4.32+/-2.20 mmol/d at prepregnancy to 6.21+/-3.72 mmol/d at T3 (P < 0.001), but only minor changes in maternal bone mineral were detected. At EL, dietary calcium and calcium absorption were not significantly different from that at prepregnancy, but urinary calcium decreased to 1.87+/-1.22 mmol/d (P < 0.001) and trabecular bone mineral density of the spine decreased to 147.7+/-21.2 mg/cm3 from 162.9+/-25.0 mg/cm3 at prepregnancy (P < 0.001). Calcium absorption postmenses increased nonsignificantly to 36.0+/-8.1% whereas urinary calcium decreased to 2.72+/-1.52 mmol/d (P < 0.001). We concluded that fetal calcium demand was met by increased maternal intestinal absorption; early breast-milk calcium was provided by maternal renal calcium conservation and loss of spinal trabecular bone, a loss that was recovered postmenses.
ABSTRACT. Objectives. Diminished bone density and a propensity to fracture with minimal trauma are common in children and adolescents with moderate to severe cerebral palsy (CP). The purpose of this study was to provide a detailed evaluation of bone mineral density (BMD) and metabolism in this population and to assess the relationship of these measures to multiple other clinical, growth, and nutrition variables.Methods. The study group consisted of 117 subjects ages 2 to 19 years (mean: 9.7 years) with moderate to severe CP as defined by the Gross Motor Functional Classification scale. Population-based sampling was used to recruit 62 of the participants, which allows for estimations of prevalence. The remaining 55 subjects were a convenience sampling from both hospital-and school-based sources. The evaluation included measures of BMD, a detailed anthropometric assessment of growth and nutritional status, medical and surgical history, the Child Health Status Questionnaire, and multiple serum analyses. BMD was measured in the distal femur, a site specifically developed for use in this contracted population, and the lumbar spine. BMD measures were converted to age and gender normalized z scores based on our own previously published control series (n > 250).Results. Osteopenia (BMD z score <؊2.0) was found in the femur of 77% of the population-based cohort and in 97% of all study participants who were unable to stand and were older than 9 years. BMD was not as low in the lumbar spine (population-based cohort mean ؎ standard error z score: ؊1.8 ؎ 0.1) as in the distal femur (mean z score: ؊3.1 ؎ 0.2). Fractures had occurred in 26% of the children who were older than 10 years. Multiple clinical and nutritional variables correlated with BMD z scores, but interpretation of these findings is complicated by covariance among variables. In stepwise regression analyses, it was found that severity of neurologic impairment as graded by Gross Motor Functional Classification level, increasing difficulty feeding the child, use of anticonvulsants, and lower triceps skinfold z scores (in decreasing order of importance) all independently contribute to lower BMD z scores in the femur.Conclusions. Low BMD is prevalent in children with moderate to severe CP and is associated with significant fracture risk. The underlying pathophysiology is complex, with multiple factors contributing to the problem and significant variation between different regions of the skeleton. Pediatrics 2002;110(1). URL: http://www. pediatrics.org/cgi/content/full/110/1/e5; cerebral palsy, bone mineral density, osteoporosis, pediatrics, bone metabolism, growth, nutrition, osteopenia.
Summary Deferasirox is a once‐daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open‐label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non‐progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11·4%) and deferoxamine (11·1%) were similar. Over 1 year, similar dose‐dependent LIC reductions were observed with deferasirox and deferoxamine. Once‐daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease.
SummaryBlood transfusion therapy is life-saving for patients with b-thalassaemia and sickle cell disease (SCD), but often results in severe iron overload. This pilot study examined whether the biomarkers of tissue injury or inflammation differ in these two diseases. Plasma malondialdehyde (MDA) was significantly increased 1AE8-fold in thalassaemia relative to control patients. In contrast, MDA in SCD was not significantly different from controls. In multivariate analysis, the strongest predictors of elevated MDA were liver iron concentration (P < 0AE001) and specific diagnosis (P ¼ 0AE019). A significant 2-fold elevation of non-transferrin bound iron (NTBI) was observed in thalassaemia relative to SCD. NTBI was not a significant predictor of high MDA in multivariate analysis. SCD patients showed a significant 2AE2-fold elevation of the inflammatory marker interleukin (IL)-6 relative to controls, and a 3AE6-and 1AE7-fold increase in IL-5 and IL-10 relative to thalassaemia. Although a-tocopherol was significantly decreased by at least 32% in both thalassaemia and SCD, indicating ongoing oxidant stress and antioxidant consumption, c-tocopherol, a nitric oxide-selective antioxidant, was increased 36% in SCD relative to thalassaemia. These results demonstrate that thalassaemia patients have increased MDA and circulating NTBI relative to SCD patients and lower levels of some cytokines and c-tocopherol. This supports the hypothesis that the biology of SCD may show increased inflammation and increased levels of protective antioxidants compared with thalassaemia.
Adults with β thalassemia major frequently have low BMD, fractures, and bone pain. The purpose of this study was to determine the prevalence of low BMD, fractures, and bone pain in all thalassemia syndromes in childhood, adolescence, and adulthood, associations of BMD with fractures and bone pain, and etiology of bone disease in thalassemia. Patients of all thalassemia syndromes in the Thalassemia Clinical Research Network, ≥6 yr of age, with no preexisting medical condition affecting bone mass or requiring steroids, participated. We measured spine and femur BMD and whole body BMC by DXA and assessed vertebral abnormalities by morphometric X-ray absorptiometry (MXA). Medical history by interview and review of medical records, physical examinations, and blood and urine collections were performed. Three hundred sixty-one subjects, 49% male, with a mean age of 23.2 yr (range, 6.1–75 yr), were studied. Spine and femur BMD Z-scores < −2 occurred in 46% and 25% of participants, respectively. Greater age, lower weight, hypogonadism, and increased bone turnover were strong independent predictors of low bone mass regardless of thalassemia syndrome. Peak bone mass was suboptimal. Thirty-six percent of patients had a history of fractures, and 34% reported bone pain. BMD was negatively associated with fractures but not with bone pain. Nine percent of participants had uniformly decreased height of several vertebrae by MXA, which was associated with the use of iron chelator deferoxamine before 6 yr of age. In patients with thalassemia, low BMD and fractures occur frequently and independently of the particular syndrome. Peak bone mass is suboptimal. Low BMD is associated with hypogonadism, increased bone turnover, and an increased risk for fractures.
Growth patterns in children with cerebral palsy were associated with their overall health and social participation. The role of these cerebral palsy-specific growth curves in clinical decision-making will require further study.
SummaryThis study aimed to determine differences in the rates of growth, endocrineand calcium-related abnormalities in the various thalassemia syndromes in North America treated with current therapies. Medical history, physical examinations and blood and urine collections were obtained from patients with all thalassemia syndromes age 6 years and older in the Thalassemia Clinical Research Network. 361 subjects, 49% male, mean age 23AE2 years (range 6AE1-75 years) were studied. Approximately 25% of children and adults, regardless of the thalassemia syndrome, had short stature. Overall growth in children was mildly affected. Final height was close to midparental height (z = )0AE73 ± 1AE24). Patients with beta thalassemia major (TM) had higher rates of hypogonadism, multiple endocrinopathies, worse hyperglycaemia, subclinical hypoparathyroidism and hypercalciuria. Hypogonadism remained the most frequent endocrinopathy and was frequently under-treated. 12AE8% of the subjects had 25 vitamin D concentrations less than 27 nmol/l and 82% less than 75 nmol/l, regardless of the thalassemia syndrome. Adolescents had lower 25 vitamin D levels than children and adults. Compared to patients with other thalassemia syndromes, those with beta TM suffered from higher rates of multiple endocrinopathies, abnormal calcium metabolism and hypercalciuria. Vitamin D abnormalities were high among adolescents.
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