Low Bone Mineral Density at Initial Diagnosis in Children and Adolescents with Graves’ Disease

Previous studies have reported reduced bone mineral density (BMD) in patients with hyperthyroidism. We assessed the association of BMD in children and adolescents with Graves’ disease (GD) after correcting for potential confounders affecting BMD such as age, sex, and pubertal status. Forty-four children and adolescents with GD and 172 age- and sex-matched healthy controls were enrolled in this study. We analyzed auxological features, BMD, and levels of thyroid hormone, thyroid-stimulating hormone, and thyroid autoantibodies. We measured BMD by dual-energy X-ray absorptiometry at the time of diagnosis in all patients. The mean age of all patients with GD (9 boys and 32 girls) was 12.1 ± 2.2 years (range, 7.0–16.0). Their initial mean free T4 and thyroid-stimulating hormone levels were 3.51 ± 1.56 ng/dL and 0.04 ± 0.03 IU/L, respectively. The mean BMD Z-scores of the lumbar spine (LS), femoral neck, and total body less head of patients with GD were significantly lower than those of control subjects. Eleven patients (26.8%) had low bone density (LS BMD Z-scores < ?2.0). To identify correlations of patient characteristics with BMD Z-scores at each site, alkaline phosphatase had a significant negative correlation with BMD Z-scores at LS and femoral neck, but not total body less head (r = ?0.441; p = 0.004 and r = ?0.351; p = 0.025, respectively). Children and adolescents with newly diagnosed GD had lower bone mass than their healthy peers. These results suggest that BMD measurement at initial evaluation may be necessary in this population.     

Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome

Summary

Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point.

Introduction

Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome.

Methods

VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry.

Results

Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3–17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2–15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), ?0.5?±?1.1; p?=?0.001) and at 3 months (?0.6?±?1.1; p?<?0.001), but not at 6 months (?0.3?±?1.3; p?=?0.066) or 12 months (?0.3?±?1.2; p?=?0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p?=?0.003). A subgroup (N?=?16; 25 %) had LS BMD Z-scores that were ≤?1.0 at 12 months. In these children, each additional 1,000 mg/m² of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, ?0.71 to ?0.07; p?=?0.017).

Conclusions

The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤?1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.     

Elevation of intact parathyroid hormone level is a risk factor for low bone mineral density in pretransplant patients with liver diseases

The purpose of this study was to investigate the frequency and risk factors for low bone mineral density (BMD) among patients awaiting liver transplantation. BMD of the lumbar spine (LS) and femoral neck (FN), measured by dual-energy X-ray absorptiometery (DEXA), were obtained in 64 pretransplant patients. We measured markers of bone metabolism including serum calcium, phosphorus, serum 25-hydroxyvitamin D (25-OH D), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), osteocalcin (OC), and urinary deoxypyridinoline/creatinine (DPD/Cr) ratio. Osteoporosis and osteopenia (low BMD) were observed in 36 patients (36/64, 56.2%), including 6 cases of osteoporosis (6/64, 9.3%) and 30 cases of osteopenia (30/64, 46.9%). Of all variables, cholestatic liver disease and elevated levels of iPTH were significantly associated with low BMD. Moreover, elevated iPTH level was identified as an independent risk factor for low BMD (P<.05, OR=1.017, 95% CI=1.001-1.032) by multivariate analysis. The median level of iPTH was increased to 55.6 pg/mL (range, 7.8-337 pg/mL) in the low BMD group, while the median level was 33 pg/mL (range, 3-162 pg/mL) in the normal BMD group (P<.05). This study revealed a high incidence of low BMD in the pretransplant patients with liver diseases. The elevated iPTH level was the predominant risk factor for low BMD. We suggest that both BMD and iPTH examinations be considered routine tests to identify the status of bone mass and bone metabolism among recipients prior to liver transplantation.     

Identification of men with reduced bone density at the lumbar spine and femoral neck using BMD of the os calcis.

We assessed the utility of os calcis (OC) bone mineral density (BMD) measurements to identify men with low BMD at the lumbar spine (LS) and femoral neck (FN). BMD was measured by dual X-ray absorptiometry (DXA). Receiver operator characteristics (ROC) analysis was applied to determine the risk of osteoporosis at the lumbar spine or femoral neck. [A total of 230 men with an average age of 59 yr were studied.] The most common reasons for referral were fracture (47%) and steroid use (46%). Twenty-six percent were osteoporotic at the LS, 21% at the FN, and 15% at the OC. Optimal classification with respect to osteoporotic measurements at the LS or FN was obtained at an OC T-score of -1.9 (BMD = 0.45 g/cm2). Osteoporosis was only weakly related to a simple cumulative risk factor score, but was strongly related to a T-score OC categorized into quartiles. Regression analysis of BMD on the major risk factors alone explained only 17% of the variance in BMD at the LS and 5% at the FN. The combination of the T-score at the OC, age, and weight provided the best model. BMD OC is superior to risk factors alone in the clinical evaluation and selection of men referred for axial densitometry.     

甲状旁腺切除术对血液透析患者合并继发性甲状旁腺功能亢进骨代谢及骨密度的影响

目的 观察甲状旁腺切除术(parathyroidectomy,PTX)对继发性甲状旁腺功能亢进(secondary hyperparathyroidism,SHPT)的维持性血液透析患者骨代谢及骨密度(BMD)的影响.方法 26例SHPT患者行PTX.术前及术后1、3、6、12、18、24个月时常规检测血钙、血磷、血清碱性磷酸酶,化学发光法检测血清全段甲状旁腺素(intact parathyroid,iPTH)、骨钙素(OC)、Ⅰ型前胶原氨基末端前肽(PINP)、β胶原蛋白(β-C TX),术前及术后24个月时双能X线法测定腰椎、股骨颈、骨盆各部位骨密度,观察患者甲状旁腺切除术前、术后骨代谢指标及骨密度变化.结果 (1)与术前比较,血清OC水平[(104.49±25.42) μg/L比(695.46±355.62) μg/L,P＜ 0.01]、PINP水平[(248.36±159.38) μg/L比(809.28±283.50) μg/L,P＜0.01]于手术3个月后明显降低,β-CTX水平于手术1个月后明显降低[(1.60±0.64) μg/L比(3.37±1.34) μg/L,P＜0.01].(2)与术前比较,术后24个月时腰椎BMD[(0.88±0.23) g/cm2比(0.78±0.23) g/cm2,P＜0.01]、股骨颈BMD[(0.96±0.19) g/cm2比(0.84±0.24) g/cm2,P＜ 0.01]及腰椎Z评分[(-1.24±0.55)比(-1.66±0.24),P＜0.01]、股骨颈Z评分[(-1.51±0.72)比(-1.93±0.40),P＜0.01]均升高.(3)相关分析显示,术前血清iPTH水平与⊿腰椎Z评分(r=0.584,P=0.002)、⊿股骨颈Z评分(r=0.400,P=0.043)呈正相关,术前血清OC水平与⊿腰椎Z评分(r=0.651,P＜0.001)、⊿股骨颈Z评分(r=0.509,P=0.008)呈正相关.结论 PTX术可以降低患者升高的iPTH、OC、PINP及β-CTX水平,增加骨密度,同时改善多项生化指标,提高患者生活质量.     

老年人腰椎正位及髓部骨密度测量结果分析

目的 了解老年腰椎及髋部骨密度(BMD)变化,并探讨不同部们测量点结果对骨质疏松症诊断的影响。方法 用法国产Lcxxos型双能x线骨密度测量仪(DEXA)对辽宁地区45-89岁老人腰椎正位及髋部骨密度测定,按年龄分组进行统计分析。结果 腰椎正位及髋部本组两性问BMD值差异有显著性(P<0.01),女性50-59岁骨量丢失较快,男性骨量丢失随年龄增长逐渐增加。且男性在75-89组腰椎BMD值保持稳定,并稍有升高趋势。各组腰椎BMD值明显高于髋部BMD值,差异有显著性(P<0.01)。腰椎BMD值诊断敏感性明显低于髋部BMD值。结论 在诊断骨质疏松症中髋部BMD值较腰椎正位BMD值更精确,且腰椎BMD值受影响因素较多,腰椎骨质增生、腰椎骨折畸形等。轻者应对异常高密区加以删除后分析,重者应避免应用压缩骨折明显或侧弯,前后凸明显,较重的腰椎增生性骨关节的腰椎前后位BMD值进行临床分析。这样才能保证诊断更准确。     

Bone mineral density in adults transplanted in childhood for liver disease

INTRODUCTION: It remains unclear whether bone mineral density (BMD) is compromised in adult life after liver transplantation (LT) during childhood. METHODS: This was a cross-sectional study of total body (TB) and lumbar spine (LS) dual-energy X-ray absorptiometry, anthropometry, and data collected, which included a physical activity questionnaire. RESULTS: Fifteen patients were enrolled. Mean age at LT was 10.6 (4.5) years (range 1.6 to 18.4). The mean posttransplant period was 12.0 (4.1) years (range 4.4 to 16.7); six were men. The mean TB BMD, 1.11 (0.12) g/cm2, was similar to LS BMD, 1.15 (0.17) g/cm2 (P=.82). The Z-score mean was lower for TB BMD, -0.92 (1.2), and LS BMD, -0.41 (1.2) (P=.22). There was no effect from gender, pretransplant cholestasis (9/15 cases), age at LT, and time since LT. BMD (Z-score) was better for those on corticosteroids (9/15 cases): TB BMD -0.42 (1.20) versus -1.77 (0.86) (P=.04); LS BMD 0.14 (1.00) versus -1.54 (1.03) (P=.03). Anthropometry Z-scores were height -0.04 (0.70), weight -0.33 (0.39), and BMI -0.32 (0.37). There was no correlation between Z-scores for BMD and any of the anthropometry parameters. CONCLUSION: Although the mean TB BMD was lower in transplanted patients than would be expected for the general population, overall BMD and anthropometry were with the normal adult ranges for adults who had undergone LT in childhood.     

Biochemical markers of bone turnover may predict progression to osteoporosis in osteopenic women: the JPOS Cohort Study

We evaluated the value of bone turnover markers, including osteocalcin (OC) and bone-specific alkaline phosphatase in the serum, and type I collagen C-terminal telopeptide and free and total deoxypyridinoline (tDPD) in the urine of fasting patients, in an attempt to predict which osteopenic women [i.e., those with ≥70% and <80% of the young adult mean (YAM) bone mineral density (BMD)] would progress to the osteoporosis level of BMD (<70% of YAM). Of the 1153 women without defects in bone metabolism who completed the 3-year follow-up, 147, 161, and 144 women were judged by dual X-ray absorptiometry to be osteopenic from baseline measurements of BMD in the spine (LS), hip (TH), and distal radius (DR), respectively. Progression to the osteoporotic level of BMD was noted for 23.8%, 16.1%, and 12.5% of the subjects with osteopenia of the LS, TH, and DR, respectively, while most of them were in the lower half of the osteopenic level of BMD at baseline. Among the subjects in this lower-level osteopenia category, a significantly higher OC level was observed for the subjects with osteoporosis progression at the LS than those without. The subjects with progression at DR showed a significantly higher tDPD level. The association between OC level and disease progression remained unchanged after adjustments for age, body size, and BMD at baseline. The subjects in the upper one-third category of OC levels showed a 6.4 fold greater risk of progression at LS (95% confidence interval, 1.8–23.1) compared with those in the lower one-third category after the adjustments for age, body size, and BMD at baseline. Receiver operating characteristics analysis showed that the area under the curve was 0.716 for the OC level in the prediction of osteoporosis progression at LS. The levels of OC and tDPD may be useful in predicting which osteopenic women will progress to osteoporosis.     

Revised Pediatric Reference Data for the Lateral Distal Femur Measured by Hologic Discovery/Delphi Dual-Energy X-Ray Absorptiometry

Lateral distal femur (LDF) scans by dual-energy X-ray absorptiometry (DXA) are often feasible in children for whom other sites are not measurable. Pediatric reference data for LDF are not available for more recent DXA technology. The objective of this study was to assess older pediatric LDF reference data, construct new reference curves for LDF bone mineral density (BMD), and demonstrate the comparability of LDF BMD to other measures of BMD and strength assessed by DXA and by peripheral quantitative computed tomography (pQCT). LDF, spine and whole body scans of 821 healthy children, 5–18 yr of age, recruited at a single center were obtained using a Hologic Discovery/Delphi system (Hologic, Inc., Bedford, MA). Tibia trabecular and total BMD (3% site), cortical geometry (38% site) (cortical thickness, section modulus, and strain-strength index) were assessed by pQCT. Sex- and race-specific reference curves were generated using LMS Chartmaker (LMS Chartmaker Pro, version 2.3. Tim Cole and Huiqi Pan. Copyright 1997-2006, Medical Research Council, UK) and Z-scores calculated and compared by correlation analysis. Z-scores for LDF BMD based on published findings demonstrated overestimation or underestimation of the prevalence of low BMD-for-age depending on the region of interest considered. Revised LDF reference curves were generated. The new LDF Z-scores were strongly and significantly associated with weight, body mass index, spine and whole body BMD Z-scores, and all pQCT Z-scores. These findings demonstrate the comparability of LDF measurements to other clinical and research bone density assessment modes, and enable assessment of BMD in children with disabilities, who are particularly prone to low trauma fractures of long bones, and for whom traditional DXA measurement sites are not feasible.     

Diagnostic evaluation of bone densitometric size adjustment techniques in children with and without low trauma fractures

Summary

Several established methods are used to size adjust dual-energy X-ray absorptiometry (DXA) measurements in children. However, there is no consensus as to which method is most diagnostically accurate. All size-adjusted bone mineral density (BMD) values were more diagnostically accurate than non-size-adjusted values. The greatest odds ratio was estimated volumetric BMD for vertebral fracture.

Introduction

The size dependence of areal bone density (BMD_a) complicates the use of DXA in children with abnormal stature. Despite several size adjustment techniques being proposed, there is no consensus as to the most appropriate size adjustment technique for estimating fracture risk in children. The aim of this study was to establish whether size adjustment techniques improve the diagnostic ability of DXA in a cohort of children with chronic diseases.

Methods

DXA measurements were performed on 450 children, 181 of whom had sustained at least one low trauma fracture. Lumbar spine (L₂–L₄) and total body less head (TBLH) Z-scores were calculated using different size adjustment techniques, namely BMD_a and volumetric BMD for age (bone mineral apparent density (BMAD)); bone mineral content (BMC) and bone area for height; BMC for bone area; BMC for lean mass (adjusted for height); and BMC for bone and body size.

Results

Unadjusted L₂–L₄ and TBLH BMD_a were most sensitive but least specific at distinguishing children with fracture. All size adjustments reduced sensitivity but increased post-test probabilities, from a pre-test probability of 40 % to between 58 and 77 %. The greatest odds ratio for fracture was L₂–L₄ BMAD for a vertebral fracture and TBLH for lean body mass (LBM) (adjusted for height) for a long bone fracture with diagnostic odds ratios of 9.3 (5.8–14.9) and 6.5 (4.1–10.2), respectively.

Conclusion

All size adjustment techniques improved the predictive ability of DXA. The most accurate method for assessing vertebral fracture was BMAD for age. The most accurate method for assessing long bone fracture was TBLH for LBM adjusted for height.     

Bone mineral density and bone histomorphometry in children on long-term dialysis

Bone mineral density (BMD) at the lumbar vertebrae (L(1)-L(4)) was assessed by dual-energy X-ray absorptiometry (DXA) in 20 children with chronic kidney disease (CKD) on dialysis, and its results were compared with bone biopsy and biochemical parameters. Biopsy specimens provided evidence of hyperparathyroid bone disease in eight cases (40%), and low bone turnover in 12 (60%). For BMD, expressed as Z-scores relative to normal, median Z-scores were -1.05 (range -2.36 to 1.06) for hyperparathyroid patients and -1.05 (range -4.40 to -0.03) for low bone turnover patients, with no statistical differences between groups (P = 0.512). In relation to BMD, of the whole sample, five (25%) had a Z-score under -2.0. When it was corrected for height, BMD was in the normal range. Additionally, there were no significant differences in single samples of serum calcium, alkaline phosphatase, phosphorus and intact parathyroid hormone (PTH) between groups with high or low bone turnover. Assessment of nutritional status, through height/age, showed that ten patients had Z-scores below -2.0 (median -2.12, range -7.13 to 0.73). In conclusion, renal osteodystrophy (ROD) seems to have a high prevalence among CKD pediatric patients, although only approximately a quarter of them developed changes in BMD. In children with CKD, measurements of bone mineral density may not be used for classification of various forms of ROD.     

Ethnic and Gender Differences in Bone Mineral Density and Bone Turnover in Young Adults: Effect of Bone Size

Generally, the incidence of osteoporotic fracture is lower in black populations and in men. These effects of ethnicity and gender may result from differences in peak bone mineral density (PBMD) and bone turnover (BT), which in turn are affected by bone size. Therefore, the aims of this study were to examine the effects of ethnicity and gender on bone mineral density (BMD) and BT in young African-Caribbean and Caucasian adults, and to adjust for the effect of bone size on BMD and BT. BMD was measured at the lumbar spine, L2–L4 (LS), total body (TB) and femoral neck (FN) by dual-energy X-ray absorptiometry in 44 blacks (16 men, 28 women) and 59 whites (28 men, 31 women) ages 20–37 years. We measured serum bone-specific alkaline phosphatase (BAP) and serum osteocalcin (OC) as markers of bone formation and urinary immunoreactive free deoxypyridinoline (ifDpd) and crosslinked N-telopeptide of type I collagen (NTx) as markers of bone resorption. To adjust the data for any differences in bone size, we calculated: (a) bone mineral apparent density (BMAD), an estimated volumetric bone density which attempts to normalize BMD measurements for bone size; and (b) bone resorption markers as a ratio to total body bone mineral content (TB BMC). Two-way analysis of variance was used to compare the effects of race and gender, and to test for any interaction between these two factors. Blacks had higher BMD compared with whites at the TB (p<0.001), LS (p= 0.0001) and FN (p= 0.0005). This increase remained significant at the LS only after calculating BMAD. Men had higher BMD at all sites (except at the LS). This increase was no longer significant at the FN after calculating BMAD, and LS BMAD was actually greater in women (p<0.0001). Blacks and whites had similar concentrations of turnover markers, but men had higher bone turnover markers than women (BAP, p<0.0001; OC, p= 0.002; ifDpd, p= 0.03; NTx, p<0.0001). This increase in bone resorption markers was no longer significant after adjusting for TB BMC (except for NTx in whites). We conclude that the skeletal advantage in blacks during young adulthood is not explained by bone size. However, it seems probable that bone size effects partially explain gender differences in BMD and bone turnover. Received: 2 February 1999 / Accepted: 2 December 1999     

Growth hormone,insulin growth factor-1, and igf binding protein-3 axis relationship with bone mineral density among healthy men

The aim of this study was to investigate serum levels of growth hormone (GH), insulin growth factor-I (IGF-I), and insulin growth factor binding protein-3 (IGFBP-3) in 363 healthy caucasian men with and without decreased bone density, who had never experienced fractures. Mean age was 51+/-8.7 years. Height and weight were measured and BMI was calculated using the formula weight (kg)/height (m(2)). Bone mineral density (BMD) was assessed: in 4 skeletal sites (lumbar spine [LS], femoral neck [FN], Ward's triangle [WT], and trochanter [T]) using dual-energy X-ray absorpsiometry (DEXA). After an overnight fasting, blood samples were taken at 8:00 a.m. Serum concentrations of GH, IGF-I, and IGFBP-3 were measured using the immunofunctional (GH) and IRMA (IGF-I and IGFBP-3) methods. The BMD at the 4 skeletal sites is expressed as mean value+/-SD in g/cm(2) and T score. Forty-four men (11%) had bone mineral density (BMD)<-2.5 SD (T score). Mean GH, IGF-I, and IGFBP-3 levels were 0.2+/-0.1, 186.1+/-177.3, and 4990+/-1460 ng/mL, respectively. There were no significant differences between men with normal BMD and men with reduced BMD concerning GH, IGF-I, and IGFBP-3 measurements. In normal men (319), mean GH, IGF-I, and IGFBP-3 levels were 0.4+/-0.1, 192+/-87, and 4960+/-1530 ng/mL, respectively. In the subgroup with reduced BMD (44), mean GH, IGF-I and IGFBP-3 levels were 0.2+/-0.1, 179+/-72 and 5230+/-1270 ng/mL, respectively. An age-dependent attenuation of GH, IGF-I, and IGFBP-3 levels was also found. No correlation was revealed between BMD and GH in the 4 skeletal sites tested. On the contrary, a positive correlation was established between BMD and IGF-I levels in 3 skeletal sites (LS, FN, T). The same was true between BMD and IGFBP-3 in 2 skeletal sites (LS, FN). In conclusion, 11% of Greek healthy males had decreased bone density. No fractures were demonstrated in any individuals. No significant differences were found between men with normal and reduced BMD, with regards to serum GH, IGF-I, and IGFBP-3, although these levels decreased with age. No correlation was found between BMD and GH levels in the 4 skeletal sites. A positive correlation was found between BMD and IGF-I levels in 3 skeletal sites and IGFBP-3 in 2 skeletal sites.     

A screening model for low bone mass in elderly Japanese men using quantitative ultrasound measurements: Fujiwara-Kyo Study

Screening for low bone mass is important to prevent fragility fractures in men as well as women, although men show a much lower prevalence of osteoporosis than women. The purpose of this study was to establish a screening model for low bone mineral density (BMD) using a quantitative ultrasound parameter and easily obtained objective indices for elderly Japanese men. We examined 1633 men (65-84 yr old) who were subjects of the Fujiwara-Kyo Study. Speed of sound (SOS) at the calcaneus was determined, and BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine (LS), total hip (TH), and femoral neck (FN). Low BMD was defined as >1 standard deviation below the young adult mean, in accordance with World Health Organization criteria. We performed receiver operating characteristic (ROC) analysis to identify a better screening model incorporating SOS and determined the optimal cutoff value using Youden index. Prevalences of low BMD at the 3 skeletal sites were 27.8% (LS), 33.5% (TH), 48.6% (FN), and 43.3% at either LS or TH. The greatest area under the ROC curve (0.806, 95% confidence interval: 0.785-0.828) and smallest Akaike's information criterion were obtained in the multivariate model incorporating SOS, age, height, and weight for predicting low BMD at all skeletal sites. This model predicted low BMD at TH with the sensitivity of 0.726 and specificity of 0.739, whereas a similar model predicted low BMD at LS with much lower validity. We conclude that the multivariate model for TH could be used to screen for low BMD in elderly Japanese men.     

A Comparison of Lumbar Spine and Lateral Distal Femur Bone Density in Girls With Rett Syndrome

Introduction/Background: Patients with Rett syndrome (RS) are at risk for low bone mineral density (BMD) and femoral fractures. In patients with RS, assessment with lateral distal femur (LDF) dual-energy X-ray absorptiometry (DXA) is recommended and clinically relevant. This study is the first to assess LDF BMD in girls with RS, and to compare LDF BMD results with lumbar spine BMD results in RS. Method Eleven girls (mean age 8.4 yr) with molecularly diagnosed RS and clinical DXA scan(s) were identified; medical charts were retrospectively reviewed. Baseline and serial lumbar spine and LDF BMD Z-scores were evaluated based on patients’ ambulation status, presence of epilepsy, and mutation type. Results At the time of first scan, 8 of 11 patients had normal lumbar spine BMD and low LDF BMD Z-scores. Two patients had fracture history. Fully ambulatory (3) patients had higher lumbar spine and LDF BMD than partially (5) and nonambulatory (3) patients. Patients with epilepsy had lower average BMD at all sites. No difference was seen in lumbar spine or LDF BMD in patients with high-risk BMD mutations. Seven patients had serial DXA scans with an average observation of 5.1 yr (range 3.1 yr to 6.2 yr). Lumbar spine BMD over time was variable, while LDF bone mass accrual occurred at a lower rate than typically developing girls. Conclusion Females with RS exhibited lower BMD Z-scores at the LDF than at the lumbar spine. LDF and lumbar spine results were discordant. Ambulatory status and the presence of epilepsy were related to BMD. LDF BMD accrual deviated from normal as patients aged.     

Physical Activity Benefits the Skeleton of Children Genetically Predisposed to Lower Bone Density in Adulthood

Both genetics and physical activity (PA) contribute to bone mineral density (BMD), but it is unknown if the benefits of physical activity on childhood bone accretion depend on genetic risk. We, therefore, aimed to determine if PA influenced the effect of bone fragility genetic variants on BMD in childhood. Our sample comprised US children of European ancestry enrolled in the Bone Mineral Density in Childhood Study (N = 918, aged 5 to 19 years, and 52.4% female). We used a questionnaire to estimate hours per day spent in total, high‐, and low‐impact PA. We calculated a BMD genetic score (% BMD lowering alleles) using adult genome‐wide association study (GWAS)‐implicated BMD variants. We used dual‐energy X‐ray absorptiometry to estimate femoral neck, total hip, and spine areal‐BMD and total body less head (TBLH) bone mineral content (BMC) Z‐scores. The BMD genetic score was negatively associated with each bone Z‐score (eg, TBLH‐BMC: estimate = –0.03, p = 1.3 × 10^?6). Total PA was positively associated with bone Z‐scores; these associations were driven by time spent in high‐impact PA (eg, TBLH‐BMC: estimate = 0.05, p = 4.0 × 10^?10) and were observed even for children with lower than average bone Z‐scores. We found no evidence of PA‐adult genetic score interactions (p interaction > 0.05) at any skeletal site, and there was no evidence of PA‐genetic score–Tanner stage interactions at any skeletal site (p interaction > 0.05). However, exploratory analyses at the individual variant level revealed that PA statistically interacted with rs2887571 (ERC1/WNT5B) to influence TBLH‐BMC in males (p interaction = 7.1 × 10^?5), where PA was associated with higher TBLH‐BMC Z‐score among the BMD‐lowering allele carriers (rs2887571 AA homozygotes: estimate = 0.08 [95% CI 0.06, 0.11], p = 2.7 × 10^?9). In conclusion, the beneficial effect of PA on bone, especially high‐impact PA, applies to the average child and those genetically predisposed to lower adult BMD (based on GWAS‐implicated BMD variants). Independent replication of our exploratory individual variant findings is warranted. © 2016 American Society for Bone and Mineral Research.     

Age trends of bone mineral density and percentile curves in healthy Chinese children and adolescents

The clinical utility of dual-energy X-ray absorptiometry (DXA) measurement requires appropriate normative values, designed to be diverse with respect to age, gender and ethnic background. The purpose of this study was to generate age-related trends for bone density in Chinese children and adolescents, and to establish a gender-specific reference database. A total of 1,541 Chinese children and adolescents aged from 5 to 19-years were recruited from southern China. Bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) were measured for the total body (TB) and total body less head (TBLH). The height-for-age, height-for-BA, and BMC-for-BA percentile curves were developed using the least mean square method. TB BMD and TBLH BMD were highly correlated. After 18 years, TB BMD was significantly higher in boys than girls. For TB BMC and TBLH BMC, gender differences were found in age groups 12 years and 16–19 years; however, the TBLH BMD was significantly different between genders >16 years. The head region accounted for 13–52 and 16–49 % of the TB BMC in boys and girls, respectively. Furthermore, the percentages were negatively correlated with age and height. This study describes a gender-specific reference database for Chinese children and adolescents aged 5–19 years. These normative values could be used for clinical assessment in this population.     

Low Bone Mineral Content and Challenges in Interpretation of Dual-Energy X-Ray Absorptiometry in Children With Mucopolysaccharidosis Types I,II, and VI

Osteoporosis has been described in animal models of mucopolysaccharidosis (MPS). Whether clinically significant osteoporosis is common among children with MPS is unknown. Therefore, cross-sectional data from whole body (WB; excluding head) and lumbar spine (LS) bone mineral density (BMD) compared with sex-, chronologic age–, and ethnicity-matched healthy individuals (Z_age), height-for-age (HAZ) Z-score (Z_HAZ) and bone mineral content (BMC) measured by dual-energy X-ray absorptiometry (DXA) in 40 children with MPS were analyzed. A subset of these children (n = 24) was matched 1:3 by age and sex to a group of healthy children (n = 72) for comparison of BMC adjusted for Tanner stage, race, lean body mass, height, and bone area. Low BMD Z-score was defined as Z-score of −2 or less. In children with MPS, 15% had low WB Z_age and 48% had low LS Z_age; 0% and 6% had low WB Z_HAZ and low LS Z_HAZ, respectively. Adjusted WB BMC was lower in MPS participants (p = 0.009). In conclusion, children with MPS had deficits in WB BMC after adjustments for stature and bone area. HAZ adjustment underestimated bone deficits (i.e., overestimated WB BMD Z-scores) in children with MPS likely owing to their abnormal bone shape. The influence of severe short stature and bone geometry on DXA measurements must be considered in children with MPS to avoid unnecessary exposure to antiresorptive treatments.     

Bone Densitometry in Canadian Children 8–17 Years of Age

Normative bone mineral density (BMD) and bone mineral content (BMC) values for the total body (TB), proximal femur (PF), and antero-posterior lumbar spine (LS) were obtained from a large cross-sectional sample of children and adolescents who were 8–17 years of age. There were 977 scans for the TB, 892 for the PF, and 666 for the LS; bone mineral values were obtained using a HOLOGIC QDR 2000 in array mode. Data are presented for the subregions of the PF (femoral neck, trochanter, intertrochanter, and the total region) and for the LS (L1–L4 and L3). Female and male values for the FN, LS (L1–L4), and the TB were compared across age groups using a two-way ANOVA. In addition, we compared the 17-year-old female values to a separate sample of young adult women (age 21). At all these sites, BMC and BMD increased significantly with age. There was no gender difference in TB BMC until age 14 or in TB BMD until age 16, when male values were significantly greater. Females had significantly greater LS BMC at ages 12 and 13, but by age 17 the male values were significantly greater. Females had significantly greater LS BMD across all age groups, however. Males had significantly greater FN BMC and BMD across all age groups. There were no significant differences in BMC or BMD at any sites between the 17- and 21-year-old women. Received: 29 September 1995 / Accepted: 1 April 1996     

Late Low-Dose Steroid Withdrawal in Renal Transplant Recipients Increases Bone Formation and Bone Mineral Density

Corticosteroids have been the most widely used immunosuppressive agents since the first clinical transplantation in the 1950s. There are few studies of late steroid withdrawal in renal transplantation and none have prospectively assessed bone mineral density (BMD). The study aim was to assess the impact of corticosteroid withdrawal, in stable renal transplant recipients, on BMD and bone turnover. BMD, osteocalcin (OC) and cross-linked telopeptide of type I collagen (CTx) were measured in 92 patients randomized into a trial of steroid withdrawal. Patients with functioning renal transplants for more than 1 year with a serum creatinine below 200 micromol/L entered the trial. All patients were on triple immunosuppression (Cyclosporin microemulsion, Azathioprine and prednisolone), corticosteroids were withdrawn at 1 mg/month. BMD was measured twice annually with serum CTx and OC. One year following withdrawal of glucocorticoids there was no significant difference in creatinine. BMD increased in the withdrawal group (2.54% per year L1-L4, p < 0.01), there was a slight reduction in the control group. Mean OC increased from 5.3 to 12.2 ng/mL (p < 0.05) in the withdrawal group, but was unchanged in the controls. No change was seen in CTx. Corticosteroid withdrawal in renal transplant recipients results in an increase in BMD with a corresponding increase in serum OC.