Bone Mineral Density Standard Deviation Score Research Articles

SAT048 Insulin Signaling Through The Insulin Receptor Increases Bone Mineral Density And Linear Growth Through Its Effects On Bone

Abstract Disclosure: R.M. Tuska: None. M.C. Okawa: None. M. Lightbourne: None. J.C. Reynolds: None. A. Layne: None. R.J. Brown: None. Context: Overnutrition and obesity associates with increased childhood growth and higher bone mineral density (BMD), whereas undernutrition associates with impaired growth and lower BMD. Increased vs decreased insulin signaling in bone may be partly responsible for these phenotypes. Patients with lipodystrophy syndromes (LD, characterized by deficient adipose tissue) have pathway selective insulin resistance (IR) causing impairment of some insulin signaling pathways while others are overstimulated by compensatory hyperinsulinemia. These patients thus serve as models of increased insulin signaling in bone without confounding by increased body mass. By contrast, patients with homozygous pathogenic variants of the insulin receptor (INSR-/-), have impairment of all insulin signaling pathways and thus model decreased insulin signaling in bone. We hypothesized that patients with LD would have tall stature and high BMD due to hyperinsulinemia, whereas those with INSR would have short stature and low BMD due to lack of insulin signaling despite hyperinsulinemia. Methods. We compared patients with genetic forms of generalized LD (GLD, (N=30), partial LD (PLD, (N=104), and INSR-/- (N=10). Whole body and site-specific (1/3 radius, Total Hip, femoral neck, and spine) DXA scans were obtained. Height Standard Deviation Scores (SDS) were calculated based on sex and age-matched normative data for patients <20 y old and based on sex-specific 20-y-old normative data for patients ≥ 20 y. Similarly, height-adjusted BMD SDS were calculated using BMDCS reference data. Blood was collected after an 8-12 hour fast for measurement of insulin. Results. All groups had hyperinsulinemia, which was highest in INSR-/- followed by PLD and CGL (423.3 mcU/ml [161.0,1000]; 31.0 mcU/ml [17.1,62.2]; 26.1 mcU/ml [11.2, 52.4]; p<0.0001). Patients with GLD and PLD had tall stature and high BMD vs the general population, whereas INSR -/- had short stature and low BMD. GLD had the greatest whole-body and site-specific BMD SDS followed by PLD and INSR -/- (Whole Body: 1.9±0.9, 0.4±1.3, -1.9± 0.1, p <0.0001; 1/3 Radius: 1.2± 1.2, 0.1± 1.6, -1.5± 1.2, p = 0.0002; Femoral Neck: 1.4±1.0, -0.7±1.3, -1.9±0.8, p <0.0001; Total Hip: 2.0±1.0, -0.3±1.3, -2.0±1.2, p <0.0001; Spine: 1.5±1.0, 0.5±1.6, -1.7±0.7, p <0.0001). All BMD SDS in each group differed from the population mean of 0, except for 1/3 radius in PLD. Similarly, GLD had the greatest height SDS followed by PLD and INSR-/- (0.5± 1.0, 0.3± 1.2, -2.5± 1.4, p<0.0001), all of which differed from the population mean. Conclusions: Patients with non-selective insulin resistance (INSR-/-) lack insulin signaling in bone, contributing to short stature and low BMD. Pathway selective insulin resistance, as observed in patients with GLD and PLD, contributes to compensatory hyperinsulinemia thus increasing insulin signaling in bone, which contributes to tall stature and high BMD. Presentation: Saturday, June 17, 2023

Insulin Signaling Through the Insulin Receptor Increases Linear Growth Through Effects on Bone and the GH-IGF-1 Axis.

Childhood overnutrition is associated with increased growth and bone mineral density (BMD) vs the opposite for undernutrition. The role of insulin receptor (InsR) signaling in these phenotypes is unclear. Rare disease patients with hyperinsulinemia and impaired InsR function (homozygous [-/-] or heterozygous [+/-] INSR pathogenic variants, type B insulin resistance [TBIR]) model increased InsR signaling, while patients with intact InsR function (congenital generalized lipodystrophy, CGL) model decreased InsR signaling. This work aimed to understand mechanisms whereby InsR signaling influences growth. A cross-sectional comparison was conducted of CGL (N = 23), INSR-/- (N = 13), INSR+/- (N = 17), and TBIR (N = 8) at the National Institutes of Health. Main outcome measures included SD scores (SDS) for height, body mass index, insulin-like growth factor (IGF)-1, and BMD, and IGF binding proteins (IGFBP)-1 and -3. INSR-/- vs CGL had higher insulin (median 266 [222-457] vs 33 [15-55] mcU/mL), higher IGFBP-1 (72 350 [55 571-103 107] vs 6453 [1634-26 674] pg/mL), lower BMI SDS (-0.7 ± 1.1 vs 0.5 ± 0.9), lower height SDS (-1.9[-4.3 to -1.3] vs 1.1 [0.5-2.5]), lower BMD SDS (-1.9 ± 1.4 vs 1.9 ± 0.7), and lower IGFBP-3 (0.37 [0.19-1.05] vs 2.00 [1.45-2.67] μg/mL) (P < .05 for all). INSR +/- were variable. Remission of TBIR lowered insulin and IGFBP-1, and increased IGF-1 and IGFBP-3 (P < .05). Patients with hyperinsulinemia and impaired InsR function exhibit impaired growth and lower BMD, whereas elevated InsR signaling (CGL) causes accelerated growth and higher BMD. These patients demonstrate that insulin action through the InsR stimulates direct anabolic effects in bone and indirect actions through the growth hormone (GH)-IGF-1 axis. TBIR patients exhibit abnormalities in the GH axis that resolve when InsR signaling is restored, supporting a causal relationship between InsR and GH axis signaling.

Bone density and body composition in small for gestational age children with adequate catch up growth: A preliminary retrospective case control study

Fetal growth patterns and birth weight (BW) have been associated with bone mineral density (BMD) and content (BMC) throughout infancy and childhood up to early adulthood. We hypothesized that in small for gestational age (SGA) children, compensatory infant catch-up growth to normal height centiles counteracts the adverse consequences of low BW on bone accrual. To evaluate BMD and BMC of SGA children born at term who experienced a normal catch-up growth as compared to children born appropriate for gestational age (AGA). We recruited 53 SGA (26 females) and 60 AGA children (27 females), aged 6 to 18years, matched for sex and body mass index (BMI). Fat mass (FM); Free fat mass (FFM); Lumbar spine and Total body less head (TBLH) BMD; BMC and BMD standard deviation scores corrected for body size (BMAD, BMAD z-score and TBLH BMD/Height) and TBLH BMC for FFM (TBLHBMC/FFM) were derived from Dual Energy X-ray absorptiometry (DXA) scans. SGA and AGA children did not differ in any auxological, body composition and bone parameters appropriately adjusted for height and FFM. BMI, FM and, remarkably, FFM were significantly correlated with bone mass parameters in both groups while no correlation was found between FM and FFM with the BW SDS in the univariate analysis. Our preliminary data demonstrate that SGA children born at term who recover from their growth deficiency through catch-up growth achieve bone mass and body composition not different from children born AGA.

The Association of Insulin-Like Growth Factor-1 With Bone Mineral Density in Survivors of Childhood Acute Leukemia

Abstract Background: The purpose of the current study is to investigate bone mineral deficit of children in survivors of childhood acute leukemia and examine the association of insulin-like growth factor-1 (IGF-1) with bone mineral density (BMD) status and the presence of osteoporosis. Methods: In a cross-sectional study of children diagnosed with different types of acute leukemia at age between 6 months and 18 years, serum IGF-1 and IGFBP-3, were assessed in relation to lumbar spine BMD (LSBMD) by using dual-energy x-ray absorptiometry and non-traumatic vertebral fracture by lateral thoracolumbar spine radiographs. Standard deviation scores (SDS) were calculated based on the age- and gender-adjusted population mean. Results: Among 189 children after completion of acute leukemia treatment, 22 (11.6%) children had LSBMD SDS less than -2.0 while 80 (42.3 %) children were diagnosed with osteoporosis. Mean areal BMD and LSBMD SDS of the subjects were 0.862±0.197 g/cm2 and -0.6±1.6, respectively. IGF-1 and IGFBP-3 were lower in children with LSBMD lower than -2.0 (P&amp;lt;0.05) and those with osteoporosis (P&amp;lt;0.05). LSBMD SDS showed linear correlation with serum IGF-1 (P=0.041). Low serum IGF-1 level (OR=0.724, P=0.042) and elder age of leukemia diagnosis (OR=1.089, P=0.023) were suggested risk factor of the occurrence of osteoporosis. Conclusions: Substantial number of survivors from childhood acute leukemia undergo bone mineral deficits, and serum IGF-1 status could be a prognostic factor associated with bone mass acquisition and future occurrence of osteoporosis.

Evaluation of bone mineral status in prepuberal children with newly diagnosed type 1 diabetes.

PurposeMany studies have reported that patients with type 1 diabetes have reduced bone mineral density (BMD). We assessed bone status in prepubertal children with type 1 diabetes mellitus (type 1 DM) at initial diagnosis and investigated factors associated with BMD.MethodsPrepubertal children (n=29) with newly diagnosed type 1 diabetes from 2006 to 2014 were included. Dual-energy X-ray absorptiometry measured regional and whole-body composition at initial diagnosis. BMD was compared with healthy controls matched for age, sex, and body mass index (BMI).ResultsThe mean age of all subjects (16 boys and 13 girls) was 7.58±1.36 years (range, 4.8–11.3 years). Initial mean glycosylated hemoglobin (HbA1c) level was 12.2%±1.9%. The mean BMD z-scores of lumbar spine, femur neck, and total body were not significantly different between patients and controls. Three patients (10.3%) had low bone density (total body BMD standard deviation score [SDS] < -2.0). To identify determinants of lumbar spine BMD z-score, multivariate regression analysis was performed with stepwise variable selection of age, pubertal status, BMI SDS, insulin like growth factor-1, and HbA1c. Only BMI SDS was significantly correlated with lumbar spine BMD z-score (β=0.395, P=0.023).ConclusionsPrepubertal children with newly diagnosed type 1 DM had similar bone mass compared to healthy peers. However, patients with low BMI should be carefully monitored for bone density in type 1 DM.

Bone Mineral Density Corrected for Size in Childhood Leukaemia Survivors Treated with Haematopoietic Stem Cell Transplantation and Total Body Irradiation

Background: Childhood leukaemia survivors treated with haematopoietic stem cell transplantation and total body irradiation (HSCT-TBI) have multiple risk factors for reduced bone mineral density (BMD) and growth failure; hence, BMD assessment must take body size into consideration. This study aimed to evaluate size-corrected BMD in leukaemia survivors treated with and without HSCT-TBI. Methods: Childhood leukaemia survivors treated with HSCT-TBI (n = 35), aged 17.3 (10.5–20.9) years, were compared with those treated with chemotherapy only, (n = 16) aged 18.5 (16.1–20.9) years, and population references. Outcome measures included anthropometric measurements and BMD by dual-energy X-ray absorptiometry. BMD was corrected for size as bone mineral apparent density (BMAD). Statistical analysis was performed by 1- and 2-sample t tests as well as regression analysis (5% significance). Results: HSCT-TBI survivors were lighter and shorter with reduced spinal heights compared with chemotherapy-only subjects and population references. Compared with population references, HSCT-TBI survivors showed lower BMD standard deviation scores (SDS) (p = 0.008), but no difference in BMAD-SDS, and chemotherapy-only survivors showed no differences in neither BMD-SDS nor BMAD-SDS. All HSCT-TBI participants with BMD-SDS <–2 had BMAD-SDS >–2. BMAD-SDS was negatively associated with age (r = –0.38, p = 0.029) in HSCT-TBI survivors. Conclusions: Size-corrected BMD are normal in HSCT-TBI survivors in young adulthood, but may reduce overtime. BMD measurements should be corrected for size in these patients to be clinically meaningful.

Factors related to decreased bone mineral density in childhood cancer survivors

The risk of osteoporosis or osteopenia is known to increase after childhood cancer treatment. The purpose of this study was to evaluate patterns of bone mineral density (BMD) and factors related to decreased BMD in childhood cancer survivors. We studied 78 patients (34 males, 44 females) treated for acute lymphoblastic leukemia, acute myelogenous leukemia or chronic myelogenous leukemia during childhood. Clinical data, laboratory finding, bone age, lumbar BMD (LBMD) and femur neck BMD (FNBMD) were investigated. Chronological age at evaluation was 11.6±3.4 yr in males and 13.0±3.3 yr in females. Primary disease, chronological age at treatment, body mass index (BMI), method of treatment (chemotherapy, radiotherapy), endocrine function, presence of chronic graft-versus-host disease (cGVHD) and relevance of BMD standard deviation score (SDS) were evaluated. LBMD and FNBMD of the subjects were -0.91±1.41 and -1.13±1.79, respectively. Twenty (25.7%) patients had LBMD SDS lower than -2. Nineteen (24.4%) patients had FNBMD SDS lower than -2. The patients treated with hematopoietic stem cell transplantation had lower LBMD SDS (-1.17±1.39 vs -0.43±1.33, P=0.025). The risk of having LBMD SDS <-2 was higher in the patients treated with glucocorticoid for cGVHD (36.6% vs 13.5%; odds ratio [OR], 3.7; P=0.020). In multivariate logistic regression analysis, longer duration of glucocorticoid treatment (OR, 1.12; 95% confidence interval [CI], 1.03-1.22) and lower BMI SDS (OR, 0.42; 95% CI, 0.21-0.83) were associated with decreased LBMD SDS. These findings suggest that prolonged glucocorticoid use and reduction in BMI are risk factors for decreased BMD in childhood cancer survivors. Anticipatory follow-up and appropriate treatment are necessary, especially for the patients with risk factors.

Growth and bone health in pediatric intestinal failure patients receiving long-term parenteral nutrition

Children with chronic intestinal failure (IF) treated with long-term parenteral nutrition (PN) may present with low bone mineral density (BMD). The cause may reflect small body size or suboptimal bone mineralization. We assessed growth and bone health in children with severe IF. Height, weight, and fracture history were recorded. The lumbar spine bone mass was measured in 45 consecutive patients (24 male subjects) aged 5-17 y receiving PN for a median of 5 y. BMD and bone mineral apparent density (BMAD) [ie, adjusted-for-height SD scores (SDSs)] were calculated. Diagnoses were short bowel syndrome in 12 patients (27%), intestinal enteropathy in 20 patients (44%), and motility disorder in 13 patients (29%). Mean (±SD) weight, height, and body mass index SDSs were -0.8 ± 1.3, -1.80 ± 1.5, and 0.4 ± 1.3, respectively. The height SDS was less than -2 in 23 children (50%). Patients with enteropathy or intestinal mucosal inflammation (associated with dysmotility or short bowel) were significantly shorter than patients without enteropathy (P = 0.007). The BMD SDS was -1.7 ± 1.6, and the BMAD SDS was -1.4 ± 1.5, independent of primary diagnosis or mucosal inflammation. Nineteen patients (42%) had low BMD (SDS less than -2.0), and 14 patients (31%) had low BMAD. In 25 patients studied at 1-2-y intervals, the BMD SDS fell significantly with time, whereas BMAD declined less, which suggested that a poor bone mineral accretion reflected poor growth. A total of 11 of 37 patients (24%) had nonpathologic fractures (P = 0.3 compared with the general population). Approximately 50% of children were short, and one-third of children had low BMD and BMAD. Children with enteropathy or intestinal mucosal inflammation are at greatest risk of growth failure. Close nutritional monitoring and bespoke PN should maximize the potential for growth and bone mass.

Factors Related to Decreased Bone Mineral Density in Childhood Cancer Survivors

The risk of osteoporosis or osteopenia is known to increase after childhood cancer treatment. The purpose of this study was to evaluate patterns of bone mineral density (BMD) and to identify factors related to the decreased BMD in childhood cancer survivors. We studied 78 patients (34 boys, 44 girls) treated for childhood cancer. Twenty (25.7%) patients had lumbar BMD (LBMD) standard deviation score (SDS) lower than -2. Nineteen (24.4%) patients had femur neck BMD (FNBMD) SDS lower than -2. The patients treated with hematopoietic stem cell transplantation had lower LBMD SDS (-1.17 ± 1.39 vs -0.43 ± 1.33, P = 0.025). The risk of having LBMD SDS < -2 was higher in the patients treated with glucocorticoid (GC) for graft-versus-host disease (GVHD) (36.6% vs 13.5%; odds ratio [OR], 3.7; P = 0.020). In multivariate logistic regression analysis, longer duration of GC treatment for GVHD (OR, 1.12; 95% confidence interval [CI], 1.05-1.20) and lower body mass index (BMI) SDS (OR, 0.59; 95% CI, 0.36-0.95) were associated with decreased LBMD SDS. These findings suggest that prolonged GC use and reduction in BMI are risk factors for decreased BMD in childhood cancer survivors. Anticipatory follow-up and appropriate treatment are necessary, especially for the patients with risk factors.

Bone Mineral Density and Body Composition in Short Children Born SGA during Growth Hormone and Gonadotropin Releasing Hormone Analog Treatment

Postponement of puberty by GnRH analog (GnRHa) in addition to GH treatment might increase adult height (AH) in short adolescents born small for gestational age (SGA). GnRHa treatment is thought to have negative effects on bone mineral density (BMD) and body composition. The objective of the study was to assess the BMD of total body (BMD(TB)), lumbar spine (BMD(LS)), bone mineral apparent density lumbar spine (BMAD(LS)), lean body mass, fat mass, and fat distribution during GH treatment, with or without an additional 2 yr of GnRHa. This was a prospective GH trial involving short SGA adolescents (≥8 yr). Eighty-eight children (50 girls) were treated until AH (GH randomized 1 or 2 mg/m(2) · d during puberty); 52 of these children received additional GnRHa. BMD and body composition were longitudinally assessed by dual-energy X-ray absorptiometry. Baseline BMD(TB) sd score (SDS) and BMD(LS) SDS were significantly reduced (both P < 0.001), but BMAD(LS) SDS was comparable with zero (P = 0.129). BMD(TB) SDS and BMD(LS) SDS improved (both P < 0.001) from the start until AH, whereas BMAD(LS) SDS remained similar (P = 0.168). At AH, 93% of patients had a normal BMD(TB), 99% a normal BMD(LS), and 98% a normal BMAD(LS) (> -2 and < +2 SDS). From the start until AH, lean body mass SDS(height) and fat mass SDS increased significantly toward zero (both P <0.001). Multiple regression analyses showed that additional GnRHa treatment had no adverse effect on the changes in BMD and body composition during GH treatment, also after correction for influencing variables. Untreated short SGA adolescents had reduced BMD(TB) and BMD(LS) but normal bone size-corrected BMAD(LS). During GH treatment, BMD(TB) and BMD(LS) increased significantly, leading to a normal adult BMD in almost all patients. Two years of GnRHa in addition to GH treatment had no adverse effect on BMD or body composition.

Effect of GnRH Analogs Leuprolide-Acetate and Triptorelin on Bone Mineral Density in Girls with Central Precocious Puberty

Purpose: The objective of this study was to evaluate the effect of gonadotropin releasing hormone analog (GnRHa) treatment on bone mineral density (BMD) in girls with central precocious puberty (CPP). Further we investigated the differences in the effect on BMD by using the GnRHa leuprolide-acetate and triptorelin. Methods: Sixty-one females with CPP were enrolled in the study, the lumbar spine BMD was measured by dual energy x-ray absorptiometry before treatment, after one year (n = 61) and after two years (n = 24) of treatment. Lumbar spine BMD standard deviation scores (SDS) were compared according to chronological age (CA) and bone age (BA) for the whole group, as well as for the group A, treated with leuprolide-acetate (n = 40), and the group B, treated with triptorelin (n = 21). Results: All subjects showed significant increment in BMD during treatment (P ˂ 0.05). Lumbar spine BMD SDS for CA and BA showed no significant changes before and during treatment. Group A and group B, within each group, showed no significant changes in lumbar spine BMD SDS for CA and BA during treatment. Conclusion: Our study suggests that lumbar spine BMD was not impaired in girls treated with GnRHa for CPP and both leuprolide-acetate and triptorelin showed comparable effects on lumbar spine BMD during treatment. (J Korean Soc Pediatr Endocrinol 2011;16:106-111)

Changes in Bone Mineral Density and Body Composition in Children with Central Precocious Puberty and Early Puberty before and after One Year of Treatment with GnRH Agonist

Background/Aims: Much concern has been raised and debated on the effects of obesity and bone mineral density (BMD) after treatment with GnRH agonist. The aim of this study was to assess BMD and body composition, especially percent body fat (%FM) based on dual-energy X-ray absorptiometry (DEXA), before and after 1 year of treatment with GnRH agonist in Korean girls. Methods: We assessed BMD and body composition in 121 Korean girls with precocious puberty before and after 1 year of treatment with GnRH agonist. BMD and body composition values were measured by using DEXA. Results: The BMD standard deviation score of each region of interest for chronological age (CA) were higher than zero, but lower than zero for bone age (BA) at baseline and the gap was decreased after 1 year of GnRH agonist treatment. The fat mass (FM) and %FM for both CA and BA were significantly higher than zero at baseline. After GnRH agonist treatment, FM and %FM decreased for CA, but increased for BA. Conclusion: Pituitary-gonadal axis suppression by GnRH agonist does not reverse the progression of bone mass acquisition and does not increase the prevalence of obesity in Korean children with precocious puberty.

Bone Mineral Density and Effects of Growth Hormone Treatment in Prepubertal Children with Prader-Willi Syndrome: A Randomized Controlled Trial

Bone mineral density (BMD) is unknown in children with Prader-Willi syndrome (PWS), but is decreased in adults with PWS. In patients with GH deficiency, BMD increases during GH treatment. The aim of the study was to evaluate BMD in children with PWS and to study the effects of GH treatment. We conducted a randomized controlled GH trial. Forty-six prepubertal children were randomized into either a GH-treated group (1.0 mg/m(2) . d) or a control group for 2 yr. At start, 6, 12, and 24 months of study, total body and lumbar spine BMD were measured by dual-energy x-ray absorptiometry, and lumbar spine bone mineral apparent density (BMAD) was calculated. Baseline total body and lumbar spine BMD sd score (SDS) were normal [mean (sd), -0.2 SDS (1.1) and -0.4 SDS (1.2), respectively]. BMADSDS, which corrects for short stature, was also normal [mean (sd), 0.40 SDS (1.1)]. Total body BMDSDS decreased during the first 6 months of GH (P < 0.0001), but increased during the second year of treatment. After 24 months of study, total body and lumbar spine BMDSDS, and the BMADSDS did not significantly differ between GH-treated children and randomized controls (P = 0.30, P = 0.44, and P = 0.47, respectively). Results were similar when corrected for body mass index SDS. Repeated measurements analysis showed a significant positive association between IGF-I SDS and total body and lumbar spine BMDSDS, but not with BMADSDS. Our results show that prepubertal children with PWS have a normal BMD. GH treatment had no effect on BMD, except for a temporary decrease of total body BMDSDS in the first 6 months.

Bone Mineral Density and Body Composition in Adolescents with Childhood-Onset Growth Hormone Deficiency

Background/Aims: The aim of the present study was to evaluate bone mineral density (BMD) and body composition of patients with childhood-onset growth hormone (GH) deficiency (GHD) treated with GH during the transition period. Methods: BMD and body composition, measured by dual-energy X-ray absorptiometry, were evaluated at final height and yearly thereafter during 2 years. Twenty-nine of the 40 patients had also been measured before start and during GH therapy. Results: Mean lumbar spine BMD and bone mineral apparent density (BMAD) as well as total body BMD and lean body mass (LBM) SD score (SDS) were significantly lower than normal at final height and during the 2 years thereafter for all patients. Final-height SDS was related to the change in height SDS as well as in LBM SDS during the first year of GH treatment. LBM SDS decreased significantly in the group of patients with GHD without GH treatment (p < 0.01, n = 19). Fat mass SDS increased in all patients. Conclusion: Mean BMD, BMAD and LBM SDS were significantly lower than normal in adolescents with childhood-onset GHD at and 2 years after the attainment of final height.

Effect of GnRH analogue on the bone mineral density of precocious or early pubertal girls

Purpose:Treatment of precocity with gonadotropin releasing hormone analogue (GnRHa) might theoretically exert a detrimental effect on the bone mass during pubertal development. We investigated the short-term changes in bone mineral density (BMD) during GnRHa treatment and the enhancement in the changes with the co-administration of GnRHa and human growth hormone (hGH). Methods:Forty girls with precocious or early puberty who were using GnRHa for more than 1 year were enrolled. Of them, 14 concurrently received hGH. Lumbar bone mineral density was measured before and after the treatment, and bone mineral density-standard deviation scores (BMD-SDSs) were compared according to chronologic age (CA) and bone age (BA), as well as according to the administration of GnRHa alone (Group I) or the co-administration of hGH and GnRHa (Group II). Results:BMDs before and after treatment were in the normal range according to CA but were significantly lower according to BA (P

Intravenous Pamidronate Therapy in Taiwanese Patients with Osteogenesis Imperfecta

Information on the long-term efficacy of intravenous pamidronate therapy in Asian patients with osteogenesis imperfecta (OI) is limited. We report our experience using pamidronate in Taiwanese patients with OI. Twenty-six patients with type I, III, or IV OI (eight males and 18 females; age range at last follow-up, 2.9-39.2 years) who received (or were currently receiving) intravenous pamidronate treatment (30mg/m2/dose, every month) were retrospectively analyzed. Patients were followed for 1.0-7.3 years over the study period from February 2000 to October 2007. The mean standard deviation score (SDS) for bone mineral density (BMD) had increased significantly from -4.72 to -3.37 (p < 0.005) after 1 year of treatment. In 16 patients evaluated after 4 years and eight after 6 years, the mean SDS continued to improve, to -2.69 (p < 0.001) and -1.54 (p < 0.005), respectively. The fracture rate decreased significantly (from 2.8 +/- 1.1 to 0.6 +/- 0.6, p < 0.001), and nine patients (35%) had no fractures while receiving treatment. The response to pamidronate was significantly better in patients with poorer initial BMD SDS (1 year: r = -0.71, p < 0.01; 4 years: r = -0.81, p < 0.01). This retrospective study suggests that Taiwanese patients with OI can benefit from pamidronate treatment, leading to a reduced incidence of fractures and increased BMD, especially in patients with poor baseline BMD.

Anthropometric, Bone Age, and Bone Mineral Density Changes after a Family-Based Treatment for Obese Children

Our objective was to identify anthropometric, bone age, and bone mineral density (BMD) changes after a family-based treatment program for obese children. We conducted a longitudinal prospective study of 50 obese children (body mass index percentage [BMI%] > or =120%) aged 9.12 +/- 1.72 years (range 6-13) at baseline. A family-based treatment program, based on inadequate feeding style with progressive modification, aerobic physical exercise increase, active parental involvement, and the use of behavioural strategies (contracting, self-monitoring, social reinforcement), was developed during a 12-month period. Anthropometric data, lumbar spine (L2-L4) BMD by dual-energy X-ray absorptiometry, bone age (BA), bone age to chronological age ratio (BA/CA), and predicted adult height (PAH) were determined at baseline and 12 months. The statistical method used was analysis of variance and the paired Student t-test. Mean BMI standard deviation score (SDS) loss was -0.61 +/- 0.76 and BMI% loss was -5.17 +/- 9.73%. Height SDS significantly decreased, BA/CA ratio also decreased significantly, and PAH change was not significant. Lumbar spine BMD SDS and BMD% did not significantly change. A family-based treatment program was effective in obese children by reducing by 5% the BMI in 1 year and increasing the activity level. Treatment reduced growth velocity and delayed bone maturation rate without affecting PAH, reflecting a situation of previous early maturation. The treatment did not modify gaining bone mass.

Long‐term effects of growth hormone (GH) treatment on body composition and bone mineral density in short children born small‐for‐gestational‐age: six‐year follow‐up of a randomized controlled GH trial

Context Alterations in the GH-IGF-I axis in short small-for-gestational-age (SGA) children might be associated with abnormalities in bone mineral density (BMD) and body composition. In addition, birth weight has been inversely associated with diabetes and cardiovascular disease in adult life. Data on detailed body composition in short SGA children and long-term effects of GH treatment are very scarce. To investigate effects of long-term GH treatment on body composition and BMD by dual energy X-ray absorptiometry (DXA) in short SGA children. Longitudinal 6-year GH study with a randomized controlled part for 3 years. At baseline, fat percentage standard deviation score (SDS) and lumbar spine BMD SDS corrected for height (BMAD(LS) SDS) were significantly lower than zero. Lean body mass (LBM) SDS adjusted for age was also reduced, but LBM adjusted for height (LBM SDS(height)) was not decreased. GH treatment induced a decrease in fat percentage SDS and an increase in BMAD(LS) SDS. LBM SDS(height) remained similar in GH-treated children, but deteriorated in untreated controls. When these untreated controls subsequently started GH treatment, their LBM SDS(height) rapidly normalized to values comparable with zero. During long-term GH treatment in short SGA children, fat percentage SDS decreased and BMAD(LS) SDS increased. These effects of GH treatment were most prominent in children who started treatment at a younger age and in those with greater height gain during GH treatment. LBM SDS(height )remained around 0 SDS in GH-treated children, but declined to low normal values in untreated controls.

Bone mineralization in children with epidermolysis bullosa

Various factors may have deleterious effects on bone health in patients with epidermolysis bullosa (EB). In a retrospective notes review, to assess bone mineralization in children with EB and to identify the relative contributions of nutrition, activity and disease severity to low bone mass. Thirty-nine children with EB [32 recessive dystrophic EB (RDEB), four Dowling-Meara EB simplex (DMEBS) and three junctional EB (JEB)] had lumbar spine bone mass measured using dual X-ray absorptiometry (GE Lunar Prodigy; GE Healthcare, Chalfont St Giles, U.K.). Seventy-six healthy children were also studied. Weight and height were recorded and mobility was rated. Children with RDEB and JEB, but not those with DMEBS, had lower bone mineral density SD scores than controls; differences remained after adjusting for the smaller body size of the patients. Bone mass was best predicted by mobility rating. Children with RDEB and JEB have low bone mass after adjusting for their smaller size, which may put them at risk for fragility fractures. Low bone mass was best predicted by the level of mobility, raising the hypothesis that improving activity or bone loading may be a potential preventive intervention in these children. However, as low bone mass may be multifactorial in these children, more detailed investigation of potential aetiological factors is required before interventions are planned.

Antiepileptic Drug-induced Osteopenia in Ambulatory Epileptic Children Receiving a Standard Vitamin D3 Supplement

Dual energy X-ray absorptiometry (DEXA) is a non-invasive, rapid, accurate and highly reproducible method for the assessment of antiepileptic drug (AED)-induced osteopenia in epileptic children. In this study, we investigated bone mineral density (BMD) using DEXA in 56 epileptic children receiving long-term AED treatment for at least 2 years. All children received AED monotherapy or polytherapy plus a standard vitamin D3 supplement (400 U/day). BMD measurements were made from lumbar spine (L2-L4) regions. Age- and sex-specific BMD SD scores were calculated for each child. Osteopenia was defined as SD scores less than -1.5. There was no significant difference in mean BMD values between epileptic children receiving monotherapy or polytherapy. The results were also compared to the age- and sex-specific BMD SD scores obtained from healthy Turkish children. Only three patients (5%) receiving AED therapy had a BMD SD score less than -1.5. This rate is relatively lower than the rates of previous studies conducted on ambulatory children on long-term AED treatment without vitamin D3 supplementation.