Bone mineral density in patients with phenylketonuria

Dual energy X-ray absorptiometry was performed in 44 patients with phenylketonuria (PKU) aged 6-29 y. The phenylalanine-restricted diet was based on a low-protein diet in combination with phenylalanine-free amino acid mixtures and phenylalanine-low casein hydrolysate in 32 patients. The 10 oldest patients were supplemented only with casein hydrolysate, and the youngest child received only the amino acid mixture. One patient has recently come off the diet. Bone mineral density (BMD) of the lumbar spine and total BMD were measured and expressed as Z-score, i.e. the difference between the BMD of the patient and the average BMD of sex- and age-matched controls divided by the standard deviation of the control group. Normal BMD was found in 24 (54%) patients. Lumbar spine BMD was decreased in 20 patients and total BMD was decreased in 14 patients. Z-scores of -1to 2.5 were found in 14 patients (32%) and Z-scores of <-2.5 in 6 patients (14%). No significant correlation was found between total or lumbar spine BMD and daily intake of phenylalanine from natural sources in the low-protein diet or the amount of phenylalanine-free amino acid mixtures per kg of body weight. A significant negative correlation was observed between both total and lumbar spine BMD Z-scores and the amount of casein hydrolysate supplementation per kg of body weight (r = - 0.45; y = 0.07 - 0.69x; p < 0.01). Long-lasting dietary restriction in patients with PKU may increase the risk of late complications of dietary therapy, such as osteoporosis or trace element deficiency. O Bone mineral density, osteoporosis, phenylalanine-low diet, phenylketonuria     

Bone mineral density in children with neurofibromatosis 1

AIM: Our aim was to detect the status of bone mineral density (BMD) in children with NF1, and thus to help the management of the skeletal complications of NF1. METHODS: Dual-energy X-ray absorptiometry (DEXA) was performed in lumbar spine, total body, proximal femur and forearm in 31 children (3.1-18 years) with NF1. Correlations among the BMD values of four regions were calculated statistically. Z-scores of lumbar- and total body-BMD were also evaluated in 24 patients at and older than 5 years. RESULTS: Eleven children had skeletal findings, including mild scoliosis in 5 patients. No case with total body-Z score <-2 was detected. Lumbar-Z score was lower than -2 in 3 out of 24 cases. Patients with any skeletal involvement of NF1 were likely to have a lumbar-BMD lower than -2 in comparison with patients with no skeletal finding (odds ratio 4; 95% CI 0.01-4.62). Proximal femur-BMD values (g/cm(2)), yet forearm-BMDs, were correlated with both lumbar- and total body-BMD, regardless of skeletal involvements of NF1. CONCLUSIONS: Our findings suggest that lumbar- or proximal femur-DEXA, rather than forearm- or total body-DEXA, could reveal significantly decreased BMD in children with NF1, especially in those with skeletal involvement of NF1.     

Changes in bone mineral density in survivors of childhood acute lymphoblastic leukemia

BACKGROUND: There is little information about factors modulating bone mineral density (BMD) in survivors of childhood acute lymphoblastic leukemia (ALL). PROCEDURE: We analyzed data from 57 survivors (26 male, 52 Caucasian) who underwent two serial quantitative computed tomography (QCT) studies of BMD. Using multiple linear regression, we evaluated the association of BMD change with demographic variables, treatment history, hormone therapy, exercise, and tobacco and alcohol use. RESULTS: The median age was 3.4 years (range, 0.9-17.4 years) at diagnosis of ALL; the median age at the first QCT (Study I) was 15.0 years (range, 10.6-31.0 years) and at the second QCT (Study II) was 18.2 years (range, 14.2-35.3 years). Mean height increased 4.7 cm and mean weight increased 8.8 kg between Studies I and II. While the mean BMD increased 9.33 mg/cc (P = 0.003), the BMD Z-score increased only slightly (0.21 SD, P = 0.035). Cortical bone density increased significantly (approximately 25.3 mg/cc; P = 0.001), but the ratio of trabecular to cortical BMD decreased significantly (P = 0.045). Factors independently associated with unfavorable BMD changes included older age at diagnosis (P = 0.001), female sex (P = 0.018), and nutritional supplementation (0.032). Alcohol (P = 0.009) was an unfavorable factor in a univariable analysis. CONCLUSIONS: Bone mineral accretion during adolescence is attenuated in childhood ALL survivors by a comparative deficit in trabecular versus cortical bone deposition. BMD is influenced favorably by exercise in early adolescence and unfavorably by the use of nutritional supplements and alcohol. These results provide new information about behavioral factors that affect bone accrual in survivors of childhood ALL and warrant definitive evaluation in a larger cohort.     

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.     

Bone mineral density in children with cerebral palsy

BACKGROUND: The purpose of the present study was to evaluate the severity of and factors related to osteopenia in children with cerebral palsy (CP). METHODS: Bone mineral density (BMD), calcium (Ca), phosphate (P), alkaline phosphatase (ALP), creatinine, parathyroid hormone (PTH) and 25-hydroxy vitamin D3 (25OHD3) concentrations were determined in 24 children with CP (15 ambulant, nine non-ambulant), aged between 10 months and 12 years (mean (+/-SD) 4.1+/-2.9 years). These vaules were compared with data obtained from a control group. RESULTS: Adjusted mean BMD values were lower in the patient group than in controls (P<0.05). However, there was no difference between BMD values of ambulant and non-ambulant patients. The Ca and P levels of the patient group were significantly higher than those of controls (P<0.05). CONCLUSIONS: The present study showed that BMD was decreased in all children with CP, but to a greater extent in non-ambulant children with CP, and immobilization is the major effective factor on bone mineralization.     

The use of bone age for bone mineral density interpretation in a cohort of pediatric brain tumor patients

Background  Skeletal bone accretion occurs throughout childhood. The integrity of this process can influence future adult bone health and the risk of osteoporosis. Although surveillance of children who are at risk of poor bone accretion is important, the most appropriate method to monitor childhood bone health has not been established. Previous investigators have proposed using bone age (BA) rather than chronological age (CA) when interpreting bone mineral density (BMD) values in children. Objective  To investigate the value of BA assessment for BMD measurement in a cohort of children at risk of poor accretion. Materials and methods  A cohort of 163 children with brain tumors who completed both a BMD assessment (quantitative computed tomography, QCT) and who had a BA within a 6-month interval were identified. The difference in BMD Z-scores determined by CA and BA was determined. The impact of salient clinical features was assessed. Results  No significant difference between CA and BA Z-scores was detected in the overall cohort (P = 0.056). However, the scores in 18 children (all boys between the ages of 11 years and 15 years) were statistically determined to be outliers from the values in the rest of the cohort. Conclusion  Interpretation of BMD with BA measurement might be appropriate and affect treatment decisions in peripubertal males.     

评价儿童青少年骨体重负荷的意义及指标选择(英文)

目的　探讨儿童青少年骨体重负荷对腰椎和髋部骨矿含量 (BMC)、骨密度 (BMD)的影响 ,并比较两指标的优次。方法　应用DXAQDR - 4 5 0 0A型扇形束骨密度仪测量长沙地区 5 4 7例 6～ 15岁儿童青少年腰椎前后位 ,仰卧侧位及髋部股骨近端的骨量。结果　不论男女 ,儿童青少年体重、体块指数 (BMI)、腰椎及髋部BMC和BMD随年龄增加而增加 (P <0 .0 5或 0 .0 1) ;体重与BMC的相关性较体重与BMD的相关性更密切 ;髋部及腰椎各部位体重标准化BMC随年龄增加而增大 ,而髋部和腰椎各部位体重标准化BMD随年龄增加反而减小。结论　 6～ 15岁儿童青少年腰椎及髋部BMC指标判断骨强度优于BMD ,尤以髋部及腰椎侧位BMC为佳。     

Bone mineral density in adolescent females treated withl-thyroxine: a longitudinal study

It has been suggested that chronic treatment withl-thyroxine (l-T4) could be implicated in reducing bone mineral density (BMD). The purpose of this longitudinal study was to determine whether appendicular and axial BMD is decreased byl-T4 treatment in adolescent girls. Thirteen adolescent girls with subclinical hypothyroidism caused by chronic lymphocytic thyroiditis were enrolled in the study at the median age of 13.4 years (range 9.2–18.1 years).l-T4 was administered in a single dose of 1–5 g/kg daily. BMD was evaluated at the distal one-third of the non-dominant radius by single photon absorptiometry (SPA) and at the lumbar spine (L2–4) by dual energy X-ray densitometry (DEXA). Osteocalcin levels were measured to assess bone turnover before and duringl-T4 treatment. Before the start of therapy, mean BMD at both the radial and lumbar level was not significantly different from that of a control group (median age 13.0 years; range 9.0–18.5 years). Duringl-T4 therapy for 2–5 years, BMD did not change at any site. Before treatment, osteocalcin levels were not significantly different from those of controls and did not change during follow up.Conclusion Long-terml-T4 therapy in adolescent girls has no adverse effect on BMD and bone turnover. Our data indicate that attainment of peak bone mass is not impaired byl-T4 administration.     

Bone mineral density in prepubertal asthmatics receiving corticosteroid treatment

OBJECTIVE: To examine whether bone mass is reduced in prepubertal, asthmatics receiving high doses of inhaled corticosteroids. METHODOLOGY: A cross-sectional comparison of lumbar spine-bone mineral density (LS-BMD) was undertaken in 76 subjects after stratifying them according to dosage and administration route of corticosteroid. RESULTS: Weight was the only independent predictor of LS-BMD (r(2) = 0.38). Children receiving greater than 800 microg/day of inhaled corticosteroid plus intermittent oral corticosteroid had a significantly lower weight-adjusted LS-BMD than children treated with 400-800 microg/day of inhaled corticosteroid (mean difference: 0.06 g/cm(2), 95% confidence interval (CI): - 0.02 to - 0.10). A significant difference in weight-adjusted LS-BMD persisted when all children receiving greater than 800 microg/day of inhaled corticosteroid, irrespective of additional oral corticosteroid treatment, were compared with children receiving 400-800 microg/day of inhaled corticosteroid (mean difference: - 0.05 g/cm(2), 95%CI interval: -0.02 to - 0.09). Bone mass was similar in children not receiving any inhaled corticosteroid and those treated with 400-800 microg/day of inhaled corticosteroid. CONCLUSIONS: A reduced bone mass in prepubertal asthmatic children receiving high doses of inhaled corticosteroids may predetermine a compromised peak bone mass and increase osteoporotic fracture risk in adulthood.     

Bone mineral density of the lumbar spine in very-low-birth-weight infants: a longitudinal study

To examine osteopenia in very low birth weight (VLBW) infants we used repeated dual-energy X-ray absorptiometry in a prospective study of lumbar spinal bone mineral density (BMD) in Japanese VLBW infants (birthweight 426–1498 g; n = 61, group 1) aged 40 weeks postconception to 3 years of age. Control subjects were Japanese infants with birthweight 1500–1999 g (group 2), 2000–2499 g (group 3), or more than 2500 g (group 4). BMD in group 1 during the early period after birth was very low, increased rapidly for 1 year, and then gradually increased until 3 years of age (r =  0.931, P < 0.0001). BMD at the age of 40 weeks postconception was 0.085 ± 0.026, 0.132 ± 0.039, 0.178 ± 0.042, and 0.196 ± 0.046 g/cm² in groups 1, 2, 3, and 4, respectively (P < 0.0001). However, at 1 and 2 years of age no differences were observed among the groups in BMD. Conclusion This study shows that lumbar spinal BMD in VLBW infants can normalize by the age of 2 years. Received: 12 May 1999 / Accepted: 11 October 1999     

Bone mineral density in malnourished children without rachitic manifestations

BACKGROUND: The purpose of this study was to determine bone mineral density (BMD) of lumbar spine in malnourished children without rachitic manifestations, before and after dietary treatment and vitamin D supplementation, and to compare with healthy children of the same community. METHODS: The subjects were 41 children with malnutrition and 21 healthy controls. None of the children had clinical, biochemical and/or radiological rickets features. The patients had moderate 15 and severe 26 malnutrition according to Gomez's criteria. Using the Wellcome Classification, marasmus was diagnosed in 16 children, kwashiorkor in 10 children. The children with malnutrition were given vitamin D supplementation. RESULTS: BMD was lower in children with malnutrition than in controls (P < 0.01). Mineralization significantly effected the severity of malnutrition (P < 0.01). BMD in kwashiorkor was similar to that of marasmus. The mean BMD level of infants receiving 400 IU of vitamin D daily was similar to that of infants receiving 800 IU of vitamin D daily at the beginning of treatment. In two supplementation groups, the BMD gradually increased during the first 3 months of treatment, but this increase in the infants receiving 800 IU of vitamin D daily was significantly higher than that in the infants receiving 400 IU of vitamin D daily. CONCLUSION: Measurements of BMD in children with malnutrition, especially severe malnutrition, are to be recommended in the initial assessment of the severity of osteopenia and in the follow up to monitor the response to therapy. Children with malnutrition should be given 800 IU of vitamin D daily. The loss of BMD must be accepted as a complication of malnutrition.     

Longitudinal monitoring of bone mineral density in thalassemic patients. Genetic structure and osteoporosis

The changes in bone mineral density (BMD) measured by single photon absorptiometry (SPA) using two observations conducted over a period of 2 years were examined in 54 thalassemic subjects [ 30 F(A)and 24 M (B)] with a chronological age ranging from 2.6 to 22.6 years and in 27 sex- and age-matched controls (C). Each category (A. B and C) was divided into three groups according to pubertal signs: pre-pubertal subjects (A1, B1 and C1): peri-pubertal subjects (A2, B2 and C2) and pubertal subjects from the first observation (A3, B3 and C3). Furthermore, each group of patients was divided into sub-groups on the basis of haematological phenotypes, those with a more severe form were called β⁰/β⁰ while those with other forms were called "others". The most significant findings were the following: the presence of a more severe reduction of the bone mineral density in patients with the β⁰/β⁰ phenotype than in patients with the "others" phenotype; patients with hypogonadism corresponded to the β⁰/β⁰ phenotype, while those with spontaneous puberty corresponded to the "others" phenotype. In conclusion, since puberty and the degree of bone mineral density are related to the haematological phenotype, puberty (spontaneous or induced) positively influences the bone mineral density only at the start of puberty, while subsequently, the degree of osteoporosis is the expression of widespread and chronic systemic damage due to the haematological phenotype.     

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.     

Risk factors for reduced areal bone mineral density in young adults with stem cell transplantation in childhood

Slightly, but significantly, reduced bone mineral density (BMD) has been detected as a late effect after stem cell transplantation (SCT) performed in childhood. The aim of the study was to evaluate the risk factors of reduced BMD after SCT in childhood. We evaluated areal BMD of 16 young adults (six males, 10 females), aged 21 yr (range 15-34) by dual-energy X-ray absorptiometry at the lumbar spine, at the femoral neck, in the total hip, and in the total body. Bone turnover rate was evaluated by markers of bone formation and resorption. Six of the 16 patients had reduced BMD with a Z-score of < or = -1 at least at one measurement site. Factors associated with reduced BMD were prepubertal status at transplant (p = 0.03), delayed pubertal growth (p = 0.03), pubertal onset gonadal hormone insufficiency (p = 0.02), and female sex (p = 0.02). Surprisingly, height in SDs and lumbar spine BMD correlated negatively (p = 0.008) in those with reduced bone mass, indicating that low areal density could not be due the small size of the vertebrae. Bone turnover markers were similar for those with normal and reduced BMD. In conclusion, 38% of the SCT long-term survivors had reduced areal BMD. Prepubertal status at transplant with pubertal onset gonadal hormone insufficiency and female sex predisposed to reduced bone mass after SCT performed in childhood.