Bone mass, biochemical markers and growth in children with chronic kidney disease: a 1-year prospective study

AIM: This study was designed to investigate bone mineral density (BMD), growth parameters and biochemical markers in children with chronic kidney disease (CKD). METHODS: Sixteen patients, 4-18 years, with CKD were prospectively followed for 1 year. Auxological data, body composition, BMD by dual-energy X-ray absorptiometry, bone age, bone turnover markers, vitamin D, parathyroid hormone (PTH), leptin, osteoprotegerin, insulin-like growth factor-I (IGF-I) and IGF binding protein-3 were measured. A questionnaire regarding bone health and diet was also performed. RESULTS: Delayed bone age was observed (n = 11) and the BMD Z-scores for total body were below zero in seven patients. However, total body BMD (TBBMD) increased in 12 patients. Most patients had increased osteocalcin and carboxy-terminal telopeptide of type I collagen, but normal alkaline phosphatase, type I procollagen intact amino-terminal propeptide and tartrate-resistant acid phosphatase 5b. Ten patients had increased PTH. Most children had normal levels of leptin, osteoprotegerin, IGF-I and IGFBP-3. Leptin, at baseline, correlated with differences in TBBMD over 1 year. CONCLUSIONS: Only seven (44%) had negative Z-scores and TBBMD increased over 1 year. Bone markers at baseline did not predict the longitudinal changes in BMD.     

Decreased bone mineral density and bone formation markers shortly after diagnosis of clinical type 1 diabetes mellitus

We recently demonstrated that children with type 1 diabetes mellitus (DM) have decreased lumbar spine bone mineral density (BMD) as early as four years after clinical diagnosis of the disease. In order to determine whether osteopenia is already present in patients very early on after diagnosis of clinical DM, we evaluated the bone mineral status of a group of newly diagnosed children (5.8 +/- 1.5 mo after diagnosis). We studied 23 prepubertal children (7 M, 16 F) with a mean chronological age of 9.5 +/- 2.2 yr and a mean glycosylated hemoglobin of 8.9 +/- 2.4%. Lumbar spine and femoral neck BMD were measured by dual X-ray absorptiometry, while bone turnover was assessed by the determination of the serum concentration of the carboxy-terminal propeptide of type I collagen (PICP) and the carboxy-terminal cross-linked telopeptide of type I collagen (N-telopeptide). Results were compared to those of age, height, and pubertal status matched controls. Lumbar spine BMD Z-scores were decreased in patients compared to controls (Z-scores of -0.89 +/- 1.2, with 10 of 22 patients showing values >1 SD below the mean). When lumbar spine Z-scores were analyzed in those patients with <3 months or > or =3 months since diagnosis of DM a significant difference was noticed between groups (-0.648 +/- 1.12 vs -1.267 +/- 1.17; p <0.02). No significant differences were noted in femoral neck BMD and total BMD between groups. Serum PICP levels were decreased when compared to controls (233.6 +/- 39.3 vs 375.9 +/- 50.7 microg/l; p <0.002), while serum N-telopeptide concentrations, although increased, were not significantly different (9.3 +/- 1.3 vs 5.7 +/- 1.5 microg/l). In summary, early on after the diagnosis of type 1 DM, children present with decreased lumbar spine BMD and decreased bone formation markers.     

Decreased lumbar spine bone mass and low bone turnover in children and adolescents with insulin dependent diabetes mellitus followed longitudinally

The effects of insulin dependent diabetes mellitus (IDDM) on bone metabolism are still not well defined. We evaluated total bone mineral content (TBMC) and bone mineral density (BMD) at the lumbar spine and femoral neck using dual X-ray absorptiometry in 26 IDDM children (15 M, 11 F) with a mean chronological age of 12.1+/-3.1 yr (range 7.1-14.2 yr). Duration of diabetes was 4.3+/-2.9 yr, with a mean glycosylated hemoglobin of 9.2+/-0.4%. BMD and TBMC standard deviation scores (Z-scores) were determined by comparing our results to controls matched for age, sex and pubertal status. BMD and bone formation and resorption markers were determined at the beginning of the study and after one year of follow up. Mean lumbar spine Z-score was -1.06+/-0.2, with negative values in 24 of 26 children (92.6%); 14/26 patients (53.8%) had a lumbar spine Z-score >1.0 SD below the mean. Mean lumbar spine Z-score remained unchanged after one year of follow up (-1.02+/-0.3). No significant differences were obtained in femoral neck BMD or TBMC between groups. No correlation was observed between lumbar spine BMD Z-scores and duration of IDDM or degree of diabetes control, as assessed by the mean glycosylated hemoglobin. Daily urinary calcium excretion was elevated in our patients initially and after one year of follow up; however, no correlation was obtained between lumbar spine BMD and 24 h urinary calcium excretion. Carboxy-terminal propeptide of type 1 collagen values and levels of urinary cross-linked N-telopeptides of type 1 collagen in the diabetic children were significantly lower than those of the matched controls. Osteoblastic activity as assessed by serum osteocalcin and by the carboxy-terminal propeptide of type I collagen and bone resorption as measured by cross-linked N-telopeptides of type 1 collagen did not correlate with the lumbar spine Z-scores. When IDDM patients were subdivided into males and females and into children with more than or less than 2 yr duration of diabetes since diagnosis, no differences between groups were found. These results suggest that insulin dependent diabetes in children is associated with low bone turnover resulting in a deficit in bone mass which may be manifested as osteopenia in the growing bone. This defect is already present in trabecular bone early on in the disease and seems not to be related to glycemic control.     

Quantitative calcaneal ultrasound parameters and bone mineral density at final height in girls treated with depot gonadotrophin-releasing hormone agonist for central precocious puberty or idiopathic short stature

To evaluate the effect of gonadotrophin-releasing hormone (GnRH) agonist treatment on bone quality at final height, we studied girls with central precocious puberty (CPP) and with idiopathic short stature (ISS). A total of 25 Caucasian girls were included: group A ( n =14) with idiopathic CPP (mean age at start 7.4 years) and group B ( n =11) with ISS (mean age at start 11.7 years). Treatment duration was 3.8 and 1.7 years respectively. The quantitative ultrasound parameters (QUS) broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus (UBIS 3000 device). Lumbar spine bone mineral density (BMD; L2–L4) was measured by dual energy X-ray absorptiometry (DXA) (Hologic QDR1000). Measurements were performed at final height and expressed as Z-scores corrected for bone age. Mean Z-scores of QUS parameters, areal BMD and volumetric BMD (BMDvol) were above –1 in both groups (group A: BUA Z-score –0.21, SOS Z-score –0.29, BMD Z-score 0.02, BMDvol Z-score 0.05, group B: BUA Z-score –0.93, SOS Z-score –0.40, BMD Z-score –0.86, BMDvol Z-score –0.68), although mean Z-scores of BUA and areal BMD in group B were significantly different from zero ( P =0.03 and P =0.02 respectively). Mean Z-score BMDvol was not significantly different from zero ( P =0.05), we found no significant difference between the groups for BMDvol ( P =0.13). Conclusion:although quantitative ultrasound parameters parameters and bone mineral density were normal in girls with central precocious puberty at final height after gonadotrophin-releasing hormone agonist treatment, mean Z-score for broadband ultrasound attenuation and areal bone mineral density were significantly different from zero and mean Z-score for volumetric bone mineral density was (just) not significantly different from zero in idiopathic short stature girls with normal puberty treated with gonadotrophin-releasing hormone agonists. Therefore we cannot say that this treatment is safe in these girls with regard to bone health.Abbreviations BMD bone mineral density - BMDvol volumetric bone mineral density - BMI body mass index - BUA broadband ultrasound attenuation - CPP central precocious puberty - DXA dual X-ray absorptiometry - GnRH gonadotrophin-releasing hormone - ISS idiopathic short stature - QUS quantitative ultrasound - SDS standard deviation score - SOS speed of sound     

Reduced bone mineral density in adult patients with Langerhans cell histiocytosis

This retrospective study evaluated bone mineral density (BMD) and bone turnover in adults with LCH. Twenty-five adult patients and 25 matched controls were evaluated with BMD measurement and indices of bone metabolism. A BMD value below the expected range for age (Z-score ≤ - 2.0) was found in 20% of patients; in particular, all postmenopausal women and men over 50-years had either osteoporosis or osteopenia. Patients with active disease had significantly lower Z-scores compared to patients with inactive disease and controls. Reduced bone turnover was found in all 14 patients treated with chemotherapy. No fractures due to osteoporosis were identified during 305.15 patient-years of follow-up.     

Bone mineral density and bone acquisition in children and young adults with cystic fibrosis: a follow-up study

OBJECTIVE: To investigate bone mineral density and bone homeostasis in cystic fibrosis (CF) and to assess changes in a 2-year period. METHODS: Thirty-eight patients with clinically stable CF (11 children, 16 adolescents, 11 young adults) were enrolled. No patient was treated with corticosteroids before or during the study. Weight and height Z scores and bone mineral density (BMD) Z-score at the femoral neck and the lumbar spine were recorded at the beginning of the study and after 2 years. Osteocalcin and cross-link excretion, both measurements of bone turnover were also measured. Correlations between BMD, bone turnover parameters, disease severity, pubertal stage, and nutritional state were calculated. The maternal BMD was also determined and related to that of the child. RESULTS: Height and weight Z scores were normal in children and below normal in adolescents. Puberty was delayed in most patients. Bone age was lower than chronological age in adolescents. Lumbar spine and femoral neck BMD Z scores were below normal in each age group. Disease severity determined by Schwachman score correlated with lumbar BMD (r = 0.45, P < 0.02). BMD Z scores did not change during 2 year follow-up. Maternal and patient lumbar and femoral BMD correlated significantly (r = 0.51, P < 0.01, and r = 0.54, P < 0.01, respectively). CONCLUSIONS: Bone deficit is present in patients with CF who have never received steroid treatment. Delay of puberty, chronic inflammation, or genetic susceptibility might be responsible for this phenomenon which was found in patients who had never received steroids and who were in relatively good clinical state.     

Risk factors for bone mineral density loss in pediatric renal transplant patients

Bone mineral density (BMD) is decreased in both adult and pediatric renal transplant recipients. To investigate the risk factors associated with this decrease in BMD post-renal transplant, we studied 33 children, aged 7-22 yr, who had received a renal transplant from 0.3 to 10 yr prior to this study. BMD analysis of the total body, spine, and femur was carried out by using dual-energy X-ray absorptiometry (DEXA). Age, weight, Tanner stage, time on dialysis prior to transplantation, cumulative corticosteroid dosage, and cyclosporin A (CsA) dosage since transplantation, and use of corticosteroid therapy prior to transplantation, were recorded. Spine, femur, and total body BMD Z-scores were greater than two standard deviations (2 SD) below the mean in 45%, 42%, and 17% of patients, respectively. Age correlated inversely with total body and spine BMD Z-scores (p = 0.001 and p = 0.008); no child under 14 yr of age had a total body or spine BMD Z-score greater than 2 SD below the mean for age. Patients at a Tanner stage of 4 or 5 had lower total body and spine BMD Z-scores than did patients at Tanner stages 1-3 (p = 0.043). Time post-transplant correlated inversely with both spine and total body BMD Z-score (p = 0.013 and p = 0.023). Only total body BMD Z-score correlated inversely with cumulative corticosteroid dose (in g, p = 0.045). BMD did not correlate with cumulative CsA dose. Black patients tended to have decreased total body BMD compared with Caucasian patients. In pediatric renal transplant patients, decreases in BMD start in adolescence. Risk factors for BMD loss in these patients include increasing age, time post-transplant, increasing Tanner stage, and ethnicity. Longitudinal studies in these patients and strategies to improve BMD are needed.     

Effects of growth hormone therapy on bone mass, metabolic balance, and well-being in young adult survivors of childhood acute lymphoblastic leukemia

Growth hormone deficiency (GHD), mostly after cranial radiotherapy (CRT), may lead to several negative effects. Young adult survivors of acute lymphoblastic leukemia (ALL) could benefit from GH therapy in different ways. Twenty ALL survivors (17.1 ± 4.3 y after diagnosis) with low bone mineral densities and/or low insulin-like growth factor-1 were included. Two of the 3 patients who only received chemotherapy had GHD. Of the 20 patients, 17 started with GH therapy and 14 completed the 2-year study period. At several time points, bone mineral density (BMD) was measured. Psychological functioning was assessed. At the start of the study, standard deviation scores of height, insulin-like growth factor-1, lumbar spine, and femoral neck BMD were all below -1. After 2 years of GH therapy, total body BMD and lean mass were significantly higher (P < 0.01 and P < 0.001, respectively), whereas the percentage fat was significantly lower (P < 0.02). Several psychological measures improved significantly after 2 years. In conclusion, GH therapy during 2 years in young adult survivors of childhood ALL did have a number of benefits, such as improvement of total body bone density and body composition. Results also suggest improvement of psychological well being. Furthermore, it also became clear that patients after chemotherapy alone should be tested for GHD.     

Bone density in the Asian thalassaemic population: a cross-sectional review

As survival improves in β-thalassaemia, osteoporosis is emerging as a significant problem. This study examines bone mineral density (BMD) of thalassaemic patients of Asian origin (age range 9.5-24 y) to evaluate the extent of problems in this group and identify potential risk factors. Eleven patients were scanned using dual-energy X-ray absorptiometry. BMD z -scores and the bone mineral apparent density (BMAD) z -scores were calculated, to correct for short stature. All but three patients had lumbar spine BMD and BMAD z -scores below the mean. Three patients had BMAD z -scores more than 2.5 standard deviations below the mean. A negative correlation between age and BMAD was seen, as was an association between endocrine disorders and decreased bone density.

Conclusion: The data confirm significant reductions in BMD in the Asian thalassaemic population, even after correcting for body size. Further research is needed to identify risk factors and means of prevention.     

Bone metabolism markers and ghrelin in boys at different stages of sexual maturity

Aim: To examine the relationship of the markers of bone formation (procollagen type I N-terminal propeptide [PINP]) and bone resorption (type I carboxyterminal telopeptide [ICTP]) with bone mineral content (BMC), bone mineral density (BMD), ghrelin and testosterone in boys during puberty.
Methods: Sixty boys were divided in three groups (20 boys in each) based on the pubertal stage (G1, I; G2–G3, II; G4–G5, III). Fasting PINP, ICTP, ghrelin and testosterone were measured. Total body BMD, lumbar BMD, lumbar apparent volumetric BMD (BMAD) and BMC were measured by DXA.
Results: PINP and ICTP values peaked at the beginning of puberty (Group II). Ghrelin was lower in Groups II and III compared to less mature boys. PINP and ICTP correlated with each other and were associated with lumbar BMAD in total group of boys. Relationships of PINP and ICTP with total BMD, total BMC and lumbar spine BMD in Group I were observed. PINP and ICTP were also correlated with testosterone in Group II and with lumbar spine BMAD in Group III.
Conclusion: These data suggest that testosterone stimulates PINP and ICTP in early puberty, while ghrelin has no direct influence on bone turnover markers in boys at different stages of puberty.     

Reduced bone mineral density and increased bone turnover in Prader-Willi syndrome compared with controls matched for sex and body mass index--a cross-sectional study

OBJECTIVES: To study bone mineral status, body composition, and biochemical markers of bone turnover in Prader-Willi syndrome (PWS). STUDY DESIGN: Eight subjects with PWS (three males, five females; mean age, 24 years [range 16-41]) were included. Each subject was compared with an age-, sex- and body mass index-matched control randomly drawn from the background population. Bone mineral density (BMD), lean body mass, and fat mass were measured. Plasma PINP, PIIINP, osteocalcin, total alkaline phosphatase, bone-specific alkaline phosphatase, C-terminal telopeptide of type I collagen, and urine cross-linked N-terminal telopeptide of type I collagen were measured as biochemical markers of bone and collagen turnover. RESULTS: The PWS patients had significantly lower whole-body BMD (mean +/- SD, 1.020 +/- 0.041 vs 1.237 +/- 0.118 g/cm(2); 2p <.01) than controls due to lower bone mineral content (BMC: 2291 +/- 607 vs 2825 +/- 409 g; 2p=.02). Resorptive and formative bone markers were significantly elevated in patients compared with controls. Plasma testosterone was low in male patients (3.50 +/- 4.97 vs 19.2 +/- 8.78 nmol/L, 2p=.05), whereas no difference in plasma estradiol was present. CONCLUSIONS: The patients had a low BMD due to a high bone turnover. This high turnover was probably linked to sex steroid deficiency.     

Comparison between broad-band ultrasound attenuation of the calcaneum and total body bone mineral density in children

We measured broad-band ultrasound attenuation (BUA) in the calcaneum using the prototype Paediatric Contact Ultrasound Bone Analyser (CUBA) and total body bone mineral density (TBBMD) using dual-energy X-ray absorptiometry (DXA) (Hologic QDR-1000W) in 58, 7 17-year-old healthy children and adolescents. Calcaneal BUA was significantly related to TBBMD ( r = 0.74, p < 0.001), and both the calcaneal BUA and TBBMD were significantly correlated with age and body weight. We conclude that calcaneal BUA reflects bone mineral density (BMD) in healthy children and adolescents; however, BMD measured by CUBA appears to be less sensitive than that measured by DXA. Since BUA reflects structural properties of bone, as well as density, it may complement radiological techniques of bone density measurement in the assessment of paediatric conditions associated with fracture risk.     

Reduced bone mineral density at diagnosis and bone mineral recovery during treatment in children with Graves' disease

OBJECTIVES: In children with Graves' disease, the prevalence of osteopenia is unknown, and the possible restoration of bone mass by antithyroid treatment has not been evaluated. The aim of this study was to prospectively evaluate the bone mineral density (BMD) and bone metabolism at diagnosis and after 1 and 2 years of medical treatment. Twenty-six children (19 girls and 7 boys) aged 11 +/- 3.4 years (range 3.4 to 15.3 years) were studied. STUDY DESIGN: BMD of the lumbar spine and proximal femur were measured by dual-energy x-ray absorptiometry. Values were compared with those of healthy children of similar age, sex, and pubertal stage. RESULTS: At diagnosis the mean BMD (standard deviation score [SDS]) was significantly reduced in both sites (P <.001) with a preferential loss of cortical bone (femoral BMD = -1.7 +/- 1.0 SDS) rather than trabecular bone (lumbar spine BMD = -0.8 +/- 1.1 SDS) (P =.003). Severe osteopenia (below -2 SDS) was found in 11 (42%) of 26 patients. Osteocalcin was significantly higher than in the control group (P <.0001), but other bone metabolism markers were normal. During treatment (n = 19) a significant gain in femoral (F = 14.7; P =.001) and lumbar spine (F = 5; P =.02) BMD (SDS) was observed, and none of the patients showed osteopenia. The annual percent change in the BMD values at the femoral (+23% +/- 11% and +6% +/- 4%, respectively, during the first and second years) and lumbar spine (+19% +/- 9% and +6% +/- 5%, respectively, during the first and second years) sites was greater during the first year than during the second year of treatment (P <.02 for femoral, P <.04 for lumbar spine). No significant age difference in BMD SD score or in BMD percent change values was observed. Osteocalcin returned rapidly to normal values, and all other bone metabolism markers remained in the normal range. CONCLUSIONS: In conclusion, severe osteopenia was observed at diagnosis in children with Graves' disease but was rapidly corrected after 1 and 2 years of treatment. Initial reduced bone mass with high bone turnover caused by hyperthyroidism was corrected after 1 year of euthyroid conditions.     

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.     

Bone mineral density is reduced in brain tumour patients treated in childhood

AIM: To determine the prevalence of low bone mineral density among children surviving brain tumours and to identify possible factors underlying impaired bone health. METHODS: Cross-sectional study; total body bone mineral density (TBBMD), fat mass (FM) and lean body mass (LBM) were measured by dual-energy X-ray absorptiometry (DXA) in 46 brain tumour patients aged from 3.8 to 28.7 y (mean 14.9 y) treated in childhood 1.4-14.8 y (mean 6.4 y) after end of treatment for brain tumour. Low bone mineral density was defined as TBBMD z score < - 2.0. RESULTS: Fifteen patients had TBBMD z scores < - 2.0, indicating a 33% prevalence of low bone density. The TBBMD z score ranged from -5.7 to 0.6 (mean -1.7). Out of several potential factors, only combined craniospinal irradiation was significantly associated with low z score (p=0.034, according to multiple regression analysis), while exclusive cranial irradiation showed a borderline statistical association (p=0.100, according to multiple regression analysis). CONCLUSION: One third of brain tumour patients treated in childhood had reduced bone mineral density. The reasons for this condition are apparently multifactorial, including craniospinal irradiation.     

Bone mineral density in children with sickle cell anemia

PURPOSE: We evaluated bone mineral density (BMD) and risk factors for poor bone mineralization in children with sickle cell anemia (SCA). PATIENTS AND METHODS: Twenty-five children with severe manifestations of SCA (frequent hospitalizations, growth delay, or need for chronic red cell transfusions) were enrolled. Bone density was assessed at lumbar spine and proximal femur with dual-energy X-ray absorptiometry (DXA), and Z-scores were calculated by comparison with age, sex, and ethnicity-specific reference data. RESULTS: The median age of the study population was 12.8 years (10.2-19.8 years). Calcium intake was inadequate in 60%, and serum 25-hydroxy vitamin D (25-OHD) level <50 nM in 74% of patients. Median Z-scores for lumbar spine (-2.3) and proximal femur (-1.7) were markedly reduced, and 64% (95% confidence interval, 43%-82%) of patients had low bone density. Z-scores were not related to age, growth delay, chronic transfusions, or ferritin level. CONCLUSION: Our results suggest that children with severe manifestations of SCA have low BMD, and possess significant deficits in dietary calcium and circulating vitamin D.     

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.     

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 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     

Growth hormone treatment enhances bone mineralisation in children with chronic renal failure

Dual energy X-ray absorptiometry of the whole body and the lumbar spine was performed to study bone mineralisation before and after 1 year of recombinant human growth hormone (rhGH) treatment in ten children with chronic renal failure. At the start, median age was 7.3 years (range 2.0–8.8 years) and median glomerular filtration rate 15 ml/min per 1.73 m² (range 7–41 ml/min per 1.73 m²). Total body mineral content (TBMC), lumbar spine mineral content (LBMC), total body bone mineral density (TBMD) and lumbar spine mineral density (LBMD) improved significantly (P < 0.05) after 1 year of treatment. Bone mineral data before and after treatment were compared with two groups of controls, i.e. ten healthy children matched for age and ten healthy children matched for height. Patients' TBMC, LBMC, TBMD and LBMD data before treatment were no different from those of height-matched controls; the same was true after 1 year of treatment except for the patients' significantly better LBMD (P < 0.05). When compared with age-matched controls, patients had significantly lower baseline TBMC and LBMC levels before treatment; after treatment LBMC was no longer different. However, there were no differences in TBMD or LBMD between patients and age-matched controls at baseline or after rhGH. Conclusion Recombinant human growth hormone treatment for 1 year results in a significant increase in both growth velocity and bone mineralisation. Comparison with height-matched controls shows a similar bone mineralisation at baseline and a better bone mineral density after treatment. Received: 10 August 2000 and in revised form 10 November 2000 and 5 January 2001 /  Accepted: 8 January 2001