Bone mineral density and metabolism in children treated with L-thyroxine.

It has been suggested that long term treatment with L-thyroxine could reduced bone mineral density (BMD). The purpose of this study was to determine whether BMD is decreased by L-thyroxine treatment in children. Dual energy X-ray absorptiometry (DEXA) was used to assess lumbar spine (L2-4) and femur neck BMD in 40 children aged 9-15 years, taking L-thyroxine (100 micrograms/m2/day) for a mean period of 1.45 +/- 0.60 years for colloid diffuse goiter. Patients were matched with controls for age, sex, weight, height and pubertal stage. BMD at both the femur neck and lumbar spine was not significantly different from that of the control group. No correlation was found between BMD values and TSH levels which is the index of tissue hyperthyroidism. BMD was also not correlated with duration of the therapy. Osteocalcin, alkaline phosphatase, calcitonin and parathormone levels were measured to asses bone turnover; none of them were significantly different from those of controls and they did not change during follow up. In conclusion we suggest that long-term L-thyroxine therapy in children has no adverse effect on BMD.     

Vitamin D receptor genotype and bone mineral density in Caucasian children with congenital hypothyroidism

Recent studies in adults suggest that some of the genetic effects on bone mineral density (BMD) and bone turnover are related to allelic variation in the vitamin D receptor (VDR) genes. It has also been suggested in patients with hyperthyroidism that the VDR genotype might influence the risk of low BMD. We examined allelic influences of the VDR gene on BMD and metabolism in 42 children with congenital hypothyroidism (CH) aged 8.5 +/- 3.4 yr treated from the neonatal period and in whom we have previously demonstrated no detrimental effects to the skeleton of prolonged L-thyroxine therapy. The prevalence of the different VDR BsmI polymorphism in this population was as expected for Caucasian children (Bb heterozygote 52%, bb homozygote 31% and BB homozygote 17%). No relationship was found between VDR genotypes and BMD (SDS), nor between VDR genotypes and serum osteocalcin levels as markers of bone formation. However, urinary D-pyridinoline levels, as markers of bone resorption, were related to VDR genotypes (p<0.04). These data indicate that the VRD genotype does have some effect on bone metabolism in children with CH but the present results give no clear indication of a detrimental effect for any given VDR genotype, at least at the BsmI restriction site, on the bone mineralization of children with CH when adequately treated with thyroxine.     

Bone mineral density and metabolism in children with congenital hypothyroidism after prolonged l-thyroxine therapy

Abstract The effect of long-term l -thyroxine (LT4) replacement therapy on bone mineral density and on biochemical markers of bone turnover were studied in children with congenital hypothyroidism (CH). Forty-four children and adolescents (mean age 8.5 ± 3.5 years) with primary CH who began LT4 replacement therapy within the first month of life were studied. Bone mineral density (BMD) of the lumbar vertebrae and the upper femoral bone was measured by dual energy X-ray absorptiometry. Serum osteocalcin (OC) and bone alkaline phosphatase were measured as markers of bone formation and urinary deoxypyridinoline was taken as a marker of bone resorption. Bone mineral densities of CH children were not different from those in age-matched controls. The biochemical markers of bone turnover were normal except for the serum OC levels which were found to be higher than in controls and positively correlated with the free thyroid hormone levels (for FT4 r = 0.42, p = 0.02). Eight CH children demonstrated low BMD values (below -1 SDS) at - 2 ± 0.7 SDS for the lumbar spine and - 1.6 ± 0.5 SDS for the femoral site. These eight children showed lower mean weight ( p < 0.05) and their dietary calcium intake tended to be less ( p < 0.06) than that seen in the normal BMD group. In conclusion, our results show that LT4 replacement therapy for 8 years is not detrimental to the skeletal mineralization of CH children. As in a healthy population, weight and current intake of calcium seem to be major determinants of bone density. Dietary recommendations, especially when calcium intake is below the recommended dietary allowance, may have to be reconsidered.     

Correlates of prepubertal bone mineral density in cystic fibrosis

AIM—To examine early factors in bone mineral accretion in cystic fibrosis (CF).
METHODS—In 22 prepubertal children with CF and mild lung disease, the relation between total body bone mineral density (BMD) and measures of body composition, biochemistry, lung function, and physical activity was studied.
RESULTS—There was a non-significant mild reduction in mean total body BMD. No relation was found between BMD and anthropometric indices, fat free soft tissue, degree of lung disease, degree of fat malabsorption, dietary energy intake, or level of physical activity. Significant impairments in physical growth were apparent in this population and were found to correlate with degree of lung disease.
CONCLUSION—A CF specific factor appears unlikely to be associated with the osteopenia commonly found in CF. Careful attention to general aspects of lifestyle and nutrition is recommended to maximise bone mineral accretion in this population.

     

Bone mineral density and bone metabolism in children treated for bone sarcomas

In adolescent bone sarcoma patients, bone mass acquisition is potentially compromised at a time in which it should be at a maximum. To evaluate the problem we measured bone mineral density (BMD) and serum markers of bone formation and resorption in a series of pediatric patients with bone tumors. BMD was measured by dual-energy x-ray absorptiometry, at clinical remission, for lumbar spine and the neck of the femur in 38 osteosarcoma and 25 Ewing's sarcoma patients. Mean age was 20.65 and 19.13 y respectively. Serum markers of bone metabolism were: OC, PICP, ICTP, 25-OH vit D and 1,25-(OH)(2) vit D, IGF-I, IGFBP-3 and intact PTH. Serum was sampled throughout anti-tumoral treatments and follow-up. We analyzed 85 samples from 59 osteosarcoma patients and 54 samples from 36 Ewing's sarcoma patients. Patients had decreased lumbar and femoral BMD. The decrease was more pronounced in pubertal patients compared with those who had completed pubertal development at the time of disease diagnosis. Multivariate analysis indicated that sex, age, weight and BMI were significant in lumbar BMD depletion. Weight and BMI were significant in femoral BMD depletion. Serum markers of bone formation (PICP and OC) and resorption (ICTP) were, throughout, lower than reference values. Significant alterations in other markers were also observed. Up to a third of osteosarcoma and Ewing's sarcoma patients in clinical remission had some degree of BMD deficit. The corresponding increased risk of pathologic bone fractures constitutes a reduction in future quality of life.     

Linear growth in early treated children with congenital hypothyroidism

Length/height was studied from birth to 6 years of age in 103 children with congenital hypothyroidism identified by the Norwegian or Swedish screening programs. We used the "infancy-childhood-puberty (ICP) growth model". This model describes normal linear growth during the first 3 years of life by an infancy component with the addition of a childhood component, the latter acting from the second half of the first year. In comparison with reference children, children with hypothyroidism had reduced growth from 6 to 12 months, and increased growth after 12 months of age. Mean onset of the childhood component of growth was delayed from 8.1 months (SD 1.9) to 10.4 months (SD 2.2) in girls, and from 8.9 months (SD 2.0) to 11.0 months (SD 2.1) in boys. Age at onset of the childhood component was correlated with age at start of treatment ( r = 0.24), and in children with more severe hypothyroidism (pretreatment serum thyroxine <40 nmol/l) inversely correlated with the L-thyroxine dose at start of treatment ( r = -0.40). Change in height standard deviation score from 1 to 3 years of age was correlated with the serum thyroxine concentration at age 1 year ( r = 0.30). The delay in the onset of the childhood component of growth and the association with age at start of treatment and initial L-thyroxine dose indicate that thyroid hormones during the first months of life are essential for normal onset of the childhood component of growth, which otherwise is assumed to be growth hormone-dependent.     

Decreased trabecular bone mineral density in patients with phenylketonuria measured by peripheral quantitative computed tomography

The bone mineral density (BMD) of 14 children, adolescents, and adults with phenylketonuria (PKU) on dietary treatment (age 5-28 y; 6F, 8M) was investigated using peripheral quantitative computed tomography (pQCT) of the distal radius. BMD of total (TBMD) and spongy bone (SBMD) were compared to those of healthy gender-, age-, weight- and height-matched controls. We found a significant decrease of SBMD in patients with PKU while TBMD was only slightly decreased, reaching no statistical significance. These results indicate minor changes of BMD in patients with PKU under treatment, which are more accentuated in the trabecular bone compartment. One additional patient who was untreated until the pQCT investigation at the age of 10 y also showed markedly decreased SBMD and TBMD.     

Initial treatment dose of L-thyroxine in congenital hypothyroidism

OBJECTIVES: To determine the optimal initial treatment dose of L-thyroxine in congenital hypothyroidism (CH) by evaluating the time course of rise of thyroxine (T(4)) and free T(4) concentrations into an established "target range" and normalization of thyroid-stimulating hormone (TSH) and to reevaluate the "target range" for T(4) and free T(4) concentrations during the first 2 weeks of CH treatment. STUDY DESIGN: Infants of birth weight 3 to 4 kg with CH (n = 47) detected by newborn screening were randomly assigned into three L-thyroxine treatment dose arms: 37.5 microg/day (group 1); 62.5 microg/day for 3 days, then 37.5 microg/day (group 2); and 50 microg/day (group 3). Serum T(4), free T(4), triiodothyronine (T(3)), free T(3), and TSH were measured before treatment and at 3 days and 1, 2, 4, 8, and 12 weeks after treatment. RESULTS: T(4) and free T(4) concentrations increased into the target range (10 to 16 microg/dL) by 3 days of therapy in infants in groups 2 and 3 and by 1 week in group 1; 50 microg/day (average 14.5 microg/kg/day) provided the most rapid normalization of TSH by 2 weeks. With the use of linear regression analysis of T(4) versus TSH or free T(4) versus TSH plots, the intercept at the lower range of normal for TSH (1.7 mU/L) showed T(4) = 19.5 microg/dL and free T(4) = 5.23 ng/dL. CONCLUSIONS: Initial dosing of 50 microg/day (12-17 microg/kg per day) raised serum T(4) and free T(4) concentrations to target range by 3 days and normalized TSH by 2 weeks of therapy. We recommend consideration of a somewhat higher "target range" of 10 to 18 microg/dL for T(4) and 2 to 5.0 ng/dL for free T(4) during the first 2 weeks of L-thyroxine treatment. After 2 weeks of treatment, the target range drops to 10 to 16 microg/dL for T(4) and 1.6 to 2.2 for free T(4).     

Correlates of prepubertal bone mineral density in cystic fibrosis.

AIM: To examine early factors in bone mineral accretion in cystic fibrosis (CF). METHODS: In 22 prepubertal children with CF and mild lung disease, the relation between total body bone mineral density (BMD) and measures of body composition, biochemistry, lung function, and physical activity was studied. RESULTS: There was a non-significant mild reduction in mean total body BMD. No relation was found between BMD and anthropometric indices, fat free soft tissue, degree of lung disease, degree of fat malabsorption, dietary energy intake, or level of physical activity. Significant impairments in physical growth were apparent in this population and were found to correlate with degree of lung disease. CONCLUSION: A CF specific factor appears unlikely to be associated with the osteopenia commonly found in CF. Careful attention to general aspects of lifestyle and nutrition is recommended to maximise bone mineral accretion in this population.     

先天性甲状腺功能减低症患儿L-甲状腺激素初始治疗剂量的研究

为探讨先天性甲状腺功能减低症(CH)患儿L_甲状腺激素(L_T4)的初次用药剂量,对确诊为CH的患儿按甲状腺扫描结果及临床分型不同给予不同剂量的L_T4,并观察其血清T3、T4、TSH浓度。结果L_T4初次用量在临床CH高于亚临床CH,在甲状腺缺如、异位、肿大及正常患儿依次减低。提示CH患儿L_T4初次用量应视病因、临床分型及血清T3、T4、TSH浓度而异。L_T4(6.4±1.29)μg/(kg·d)是较合适的初次治疗剂量。     

定量超声技术对儿童骨代谢状况的评估价值

目的 评价定量超声检测技术在了解学龄期儿童骨代谢状况中的价值.方法 采用定量超声仪对1750名学龄期儿童进行左侧胫骨声波速度(SOS)测量,同时评价体格发育指标及测定骨碱性磷酸酶(BALP),研究SOS与年龄、性别、体格发育指标、BALP的关系.结果 研究对象营养状况较好,其中7～9岁男童肥胖的检出率较高;SOS值随年龄增长而逐渐增高,但男、女儿童出现SOS值快速增长的年龄阶段不同;不同的BALP活性对应的SOS值差异无统计学意义;体质量、身高与SOS值成显著正相关(P<0.05);10～12岁女性肥胖儿童的SOS值明显高于同年龄的非肥胖儿童(P均<0.05);多元回归分析发现身高是影响学龄期儿童SOS值的重要因素(J<0.05).结论 定量超声检测能用于反映骨代谢状况.这一技术在监测学龄期儿童骨骼发育中有良好的应用前景,但评价学龄期儿童的骨代谢状况应考虑到多种因素的影响,利用多种检测技术综合评价.     

Sustained attention problems in children with early treated congenital hypothyroidism

Sustained attention was studied in 48 children with early treated congenital hypothyroidism and 35 healthy controls, using a computer-paced and a self-paced continuous performance task. The performance of the patients, particularly those in the low T4 group (38 patients with T4 levels < 50 nmol/1 at neonatal screening), declined in the final stage of the computer-paced task, suggesting a problem in remaining attentive over time. The performance of all children declined in the first and improved in the final stage of the self-paced task. This pattern was most pronounced in the low T4 group, reflecting greater variability in their task performance over time, again indicating a problem in sustaining attention. No correlation was found between onset of treatment and sustained attention. The small size of the intermediate T4 group (10 patients with T4 levels ≥ 250 nmol/1 at neonatal screening) made the results more difficult to interpret and may have concealed a problem with sustained attention in this group.     

Osteoporosis in children with severe congenital neutropenia: bone mineral density and treatment with bisphosphonates

A high incidence of decreased bone mineral density (BMD) has been described in patients with severe congenital neutropenia (SCN). The objectives of the study are to describe changes in BMD in children with SCN treated with granulocyte colony-stimulating factor and evaluate the response to treatment with bisphosphonates in those who had osteoporosis. A prospective open-label study was performed evaluating BMD and metabolism in 9 Chilean patients with SCN, administrating bisphosphonates in those with osteoporosis. Follow-up ranged between 7 months and 3.5 years. Six out of 9 patients had reduced BMD on initial assessment: 3 had osteoporosis (z score <-2) and 3 had osteopenia (z score <-1). Four children presented vertebral fractures. Two presented osteopenia on follow-up without clinical symptoms. Five patients were treated with bisphosphonates, increasing their BMD z score (mean increase 1.2, range 0.27 to 2.62). z Score of hydroxyproline/creatinine ratios, which was elevated in 4 patients with osteoporosis, decreased during treatment (mean decrease 2.18, range 1.56 to 2.53). Four patients remodeled and reexpanded fractured vertebrae during treatment. No side effects of bisphosphonates were seen on follow-up. Osteoporosis is an important comorbidity in SCN patients probably due to increased bone resorption. Bisphosphonates seem to be an effective treatment for osteoporosis in these patients.     

Reproducibility of DXA measurements of bone mineral density and body composition in children

Background  The technique of X-ray-based dual photon absorptiometry (DXA) is frequently used in children for the detection of changes in bone mass or body composition. Such changes can only be considered real if the uncertainties arising from the measurement technique are exceeded. Objective  Our objectives were twofold: (1) to determine the reproducibility of bone mineral density (BMD) measurements in children at the spine and the hip and from the whole body, as well as of whole-body measurements of mineral mass, lean body mass and fat mass in children; and (2) to estimate, from the measured precision, the time interval that needs to elapse before a statistically significant change in a DXA variable can be detected. Materials and methods  The reproducibility of techniques for the measurement of BMD and body composition using DXA was measured in 15 young children (9 girls and 6 boys) and 17 older children (9 girls and 8 boys). Results  Reproducibility was derived from the standard deviation of three repeated measurements of spine BMD, total hip BMD, whole-body BMD (WBBMD), whole-body bone mineral content (WBBMC), lean mass and fat mass. Technique precision was better than 0.01 g cm⁻² for spine BMD and for WBBMD. Hip BMD measurements were slightly less precise, particularly in younger children (0.013 g cm⁻²). For body composition variables, technique precision was 13 g for WBBMC, 201 g for lean body mass and 172 g for fat mass in younger children. Technique precision for older children was 18 g, 251 g and 189 g for the corresponding variables. Predictions showed that the absence of a normal increase in WBBMC in a small-for-age girl could be established after 12 months. For spine BMD, a significant increase should be observable after 6 months for boys over the age of 11 years. For younger boys, more than 12 months has to elapse before anticipated changes can be detected with confidence. Conclusion  The time intervals required to elapse before decisions can be made concerning the significance of observed differences between successive measurements of BMD or body composition in children depend upon the age of the child.     

The effect of life-long thyroxine treatment and physical activity on bone mineral density in young adult women with congenital hypothyroidism

OBJECTIVE: Normalization of plasma thyrotropin in T4-supplemented patients with thyroidal congenital hypothyroidism (CH) requires elevated plasma FT4-concentrations compared to patients with acquired thyroidal hypothyroidism. We investigated bone mineral density (BMD) in patients with CH. PATIENTS AND METHODS: BMD was measured in 14 adult women with thyroidal CH and nine age-matched female controls. RESULTS: There were no significant differences between patients and controls for femoral neck bone mineral content (BMC) (38.6 vs 37.6 g), BMD (0.98 vs 1.01 g/cm(2)), T-score (0.1 vs 0.3 SD) and z-score (0.1 vs 0.3 SD) and for spine BMC (63.1 vs 71.9 g). The differences in spine BMD (0.97 vs 1.09 g/cm(2)), T-score (-0.7 vs 0.4 SD) and z-score (-0.5 vs 0.6 SD) were significant (p = 0.025, p = 0.023, and p = 0.021, respectively). CONCLUSIONS: Although BMD in patients with CH was slightly lower compared to controls, all scores were within the reference range. This does not support the hypothesis that the upwards shifted plasma FT4-concentrations in patients treated for CH have a deleterious effect on BMD.     

Evaluation of bone mineral density in children with diabetes mellitus

Multiple studies have documented reduction in peripheral bone mass in children with insulin dependent diabetes mellitus (IDDM). In this study, the bone mineral density (BMD) of the lumbar vertebrae (L₂–L₄) was measured by dual photon absorptiometry in 14 female and 16 male diabetic patients of age 11 to 16 years with varying clinical duration. Twenty three children between 11 to 16 years with normal anthropometric measurements between 10th and 97th percentile and no known history of metabolic bone disease served as a control group. BMD values, weight, height, body mass index, metabolic, biochemical and growth parameters of the study group were compared with those of the control group. BMD (L₂ AP 0.732±0.15 gm/cm², L₂ lateral 0.534 ±0.09 gm/cm²in the study group and 0.812±0.63 gm/cm² and 0.619±0.20 gm/cm² in the control group) and osteoccalcin (10.10±3.40 ng/ml and 23.12±2.74 ng/ml in diabetes and control respectively) levels were significantly lower in diabetic patients (p<0.05, p<0.01 respectively). Within the study group BMD correlated positively with age but not with the duration of the disease nor with the level of metabolic control.