Lumbar Bone Mineral Density Z-scores Research Articles

Association between Low Bone Mineral Density and Pain in a Prospective Cohort of Adults with Sickle Cell Disease: Preliminary Results from the SCD Bone Pain Study

Background: Osteonecrosis (ON), a prevalent skeletal complication of sickle cell disease (SCD), typically associates with severe chronic pain, frequent acute care utilization, and permanent disability. We previously showed that low bone mineral density (BMD) independently associates with hip ON and chronic pain in a pediatric SCD cohort. We now present preliminary data on the association between low BMD and pain in a prospective cohort of adults enrolled in the SCD Bone Pain Study (NCT05283148). Methods: Written informed consent was obtained from all participants, who were recruited from ambulatory adults with SCD seen at the University of California Davis Comprehensive Cancer Center. All participants underwent dual-energy X-ray absorptiometry (DXA) scans of their lumbar spine, left hip, and left forearm. Vertebral fractures were assessed by thoracolumbar morphometry in the DXA scanner. All participants also completed the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) Pain Impact questionnaire. We used linear regression to evaluate the association between ASCQ-Me pain scores and low BMD (categorically defined as BMD Z-score ≤ -2 at any DXA site). We also used linear regression to determine the association between ASCQ-Me pain scores and continuous total hip and lumbar spine BMD Z-scores. Lastly, we evaluated the impact of other covariates on pain scores, with low BMD or BMD Z-scores included in the least absolute shrinkage and selection operator (LASSO, no shrinkage). Results: Thirty adults (median age 34.5 years [20-67 years]) completed the study between Nov 2022-Jul 2023. Baseline characteristics are summarized in Table 1. There was a borderline significant association between low BMD and lower (worse) pain scores (p=0.077). Continuous BMD Z-scores of the total hip (p=0.081) and lumbar spine (p=0.024) were independently associated with higher (better) pain scores. In addition to low BMD, only white blood cell count (WBC), indirect bilirubin, and vitamin D were identified as possible covariates (all had non-zero coefficients in LASSO analysis). Low BMD was significantly associated with pain (p=0.024), even after adjusting for WBC, indirect bilirubin, and vitamin D (Table 2). Similarly, we found that higher hip (p=0.059) and lumbar (p=0.027) BMD Z-scores were associated with higher (better) pain scores, despite adjusting for the same confounders. Discussion: We found low BMD in 12 of 30 (40%) adults enrolled in the SCD Bone Pain Study. Like other chronic hemolytic anemias, compensatory increased erythropoiesis leads to trabeculae degradation, cortical bone thinning, and eventual low bone mass. Lumbar vertebrae comprises mostly of trabecular bone, while the hip joint has mostly cortical bone. This might explain why mean lumbar BMD Z-scores were lower than hip BMD Z-scores (Table 1), and why lumbar spine BMD Z-scores directly and significantly correlated with pain scores (Table 2). These preliminary data suggest that pain is more prevalent in SCD adults with low BMD than those with normal BMD as we previously reported in a pediatric SCD cohort. Pain scores decrease (worsen) with increasing WBC, which suggests an inflammatory component to chronic SCD pain. Contrary to expectation, higher indirect bilirubin (a marker of increased hemolysis) significantly correlated with higher (better) pain scores. Similarly, higher vitamin D (a proxy for bone health) correlated with lower (worse) pain scores, though this association was non-significant. The reason(s) for these counterintuitive associations between pain scores, indirect bilirubin, and vitamin D levels is currently unknown. Limitations include a small sample size, though using the LASSO method for multivariate regression adjusted for this. Further, low BMD causality could not be determined at this time. Recruitment is ongoing with an enrollment target of 50 adults with SCD by Nov 2023. Analysis are ongoing to determine if SCD-modifying therapies will impact the association between low BMD and pain. Bone biomarker studies are also pending. Further, the thoracolumbar morphometry is still undergoing radiologic review, so we can further assess how vertebral compression fractures (i) correlate with pain scores, and/or (ii) attenuate the association between low BMD and pain. Identifying and treating risk factors for low BMD may alleviate bone pain and potentially improve quality of life for all people with SCD.

Factors Associated with Low Bone Mineral Density at the Time of Diagnosis in Children with Celiac Disease

It has been reported that bone mineral density (BMD) is decreased in children with Celiac disease (CD) compared to their healthy peers. The aim of this study was to reveal possible risk factors for low BMD in Turkish children newly diagnosed with CD. Eighty-six patients (2-18 years old) with CD were included in this retrospective study. The relationship between their lumbar BMD z-scores calculated according to their chronological age (CA) and height age (HA) and their clinical, laboratory [biochemical parameters, tissue transglutaminase antibody-IgA (TTGA) levels, human leukocyte antigen (HLA) types] and histopathological parameters were evaluated. The mean age of the patients at diagnosis was 8.06±4.08 years. The BMD z-score CA was ≤-2 standard deviation (SD) in 26.7% of the patients. The BMD z-score HA was ≤-2 SD in 12.8% of the patients. The BMD z-score HA only correlated with their age at diagnosis of CD (rs value 0.269). However, there was no statistically difference between the BMD z-score HA >-2 SD and ≤-2 SD subgroups regarding their clinical, laboratory and histopathological parameters. Low BMD is common in children with newly diagnosed CD. Age at diagnosis, gender, body size, Celiac symptoms, biochemical parameters, TTGA level, HLA type, and histopathological stage had no predictive values in terms of low BMD in this patient group.

Effect of gender, diabetes duration, inflammatory cytokines, and vitamin D level on bone mineral density among Thai children and adolescents with type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is considered a risk factor for osteoporosis in adults; however, studies in bone mineral density (BMD) in children with T1DM reported conflicting results. The aim of this study was to compare BMD between T1DM youth and healthy controls, and to identify factors that affect BMD in T1DM youth. One hundred T1DM youths and 100 healthy controls (both groups aged 5-20 years) were recruited. BMD of total body, lumbar (L2-4), femoral neck, and total hip were assessed using dual energy X-ray absorptiometry. Blood investigations, including hemoglobin A1c (HbA1c), 25-hydroxyvitamin D, and inflammatory cytokines, were performed. Forty-four boys and 56 girls with T1DM were enrolled [mean age 14.5 ± 2.7 years, median (IQR) duration of T1DM 5.80 (2.97-9.07) years, and mean HbA1c entire duration 9.2 ± 1.4%]. T1DM girls had a lower height Z-score than control girls (p < 0.05), and 25-hydroxyvitamin D level was higher in T1DM youth than in controls (p < 0.001). After adjusting for pubertal status, height Z-score, and 25-hydroxyvitamin D, T1DM youth had a significantly lower lumbar BMD Z-score and femoral neck BMD than controls (p = 0.027 and p = 0.025, respectively). We also found that T1DM boys had a significantly lower lumbar BMD Z-score (p = 0.028), femoral neck BMD (p = 0.004), and total hip BMD (p = 0.016) than control boys. In contrast, these significant differences were not found in T1DM girls. Factors affecting BMD were different between T1DM boys and girls, and among different BMD sites. IL-13 was positively correlated with BMD in the total cohort and among girls. In boys - IL-2 and 25-hydroxyvitamin D were positively associated with BMD, and duration of diabetes was found to negatively affect BMD. Deleterious effect of T1DM on BMD is gender specific. The longer the duration of T1DM, the greater the deficit in BMD found among boys with T1DM.

Higher Peptide YY Levels Are Associated With Lower Bone Mineral Density in Low Weight Adolescent Girls With Avoidant/Restrictive Food Intake Disorder

Background: Avoidant/Restrictive Food Intake Disorder (ARFID) is a condition characterized by lack of interest in eating or food, sensory sensitivity, and/or fear of aversive consequences of eating; as opposed to the body image disturbance and fear of weight gain that characterize anorexia nervosa (AN). While appetite regulating hormones and their associations with bone mineral density (BMD) have been well studied in AN, little is known regarding BMD and its association with appetite regulating hormones in ARFID. Peptide YY (PYY), a gut derived anorexigenic hormone, acts via the Y2 receptor to inhibit osteoblastic activity in mammals. In AN, levels of PYY are higher than in healthy controls (HC) and are negatively associated with BMD. We hypothesized that similar to AN, low-weight female adolescents with ARFID would have lower BMD and higher PYY levels than in HC and that PYY levels would be inversely associated with BMD. Methods: We studied 24 adolescent females (10 low weight with ARFID and 14 HC). BMD variables were measured by Dual-Energy X-ray Absorptiometry. We performed cross sectional analysis to compare BMD and fasting PYY levels between low weight ARFID and HC and to determine the relationship between BMD and PYY levels. Results: ARFID and HC were 15.1±2.9 (mean ± SEM) and 17.1±3.8 years old, respectively (p=0.178), with mean BMI Z-scores of -1.74±0.88 kg/m2 and 0.24±0.51 kg/m2, respectively (p<0.0001). Total body BMD Z-scores were significantly lower in ARFID (-1.59±1.19, n=10) compared to HC (-0.41±1.11, n=14) (p=0.022), and lumbar BMD Z-scores were numerically lower in ARFID (-1.13±1.40, n=9) vs. HC (-0.44±0.86, n=14) (p=0.212). Mean PYY levels trended higher in ARFID (104.6±39.9 pg/ml, n=8) vs. HC (71.4±24.5 pg/ml, n=9) (p=0.054). In a combined analysis of participants with ARFID and HC, PYY levels were negatively correlated with lumbar BMD and BMD Z-scores (r=-0.52, p=0.038 and r=-0.54 p=0.031, n=16). In multivariable regression analysis, PYY remained a primary determinant of lumbar BMD after adjusting for age and height (p=0.035, β= -0.36) and a borderline significant predictor of lumbar BMD Z-scores after adjusting for height (p=0.064, β=-0.5). Similar associations were noted within the ARFID group alone, with PYY being a significant predictor of lumbar BMD (p=0.031, β=-0.97) after adjusting for age and height. Conclusion: Female adolescents with low-weight ARFID have lower BMD and a trend toward higher levels of PYY compared with HC. Increased PYY levels may contribute to the lower BMD observed in ARFID. These findings are an initial step in understanding the neuroendocrine dysregulation in low weight adolescents with ARFID, which may predict bone outcomes in this condition.

Growth, puberty, and bone health in children and adolescents with inflammatory bowel disease

BackgroundEndocrine complications such as impaired growth, delayed puberty, and low bone mineral density (BMD) can be associated with inflammatory bowel disease (IBD) in children and adolescents. This study was performed to investigate the frequency, characteristics, and outcomes of endocrine complications of IBD in children and adolescents.MethodsThis study included 127 patients with IBD diagnosed before 18 years of age [117 with Crohn disease (CD) and 10 with ulcerative colitis (UC)]. Growth profiles, pubertal status, 25-hydroxyvitamin D3 [25(OH)D3] levels, and BMD were reviewed retrospectively.ResultsShort stature was observed in 14 of 127 (11.0 %) with a mean height-SDS of -2.31 ± 0.72. During a 2-year follow-up period, height-SDS did not significantly improve, while weight-SDS significantly improved. Among 109 patients who were older than 13 (girls) or 14 (boys) years of age during the study period, 11 patients (10.1 %) showed delayed puberty, which was associated with low weight-SDS. Vitamin D deficiency was documented in 81.7 % (94/115) with the average 25(OH)D3 level of 14.5 ± 7.0 ng/mL. Lumbar BMD Z-score was below − 2 SDS in 25 of 119 patients (21.0 %). Height-SDS, weight-SDS, and body mass index (BMI)-SDS were lower in patients with osteoporosis than those without osteoporosis. When pediatric CD activity index scores were high (≥ 30), weight-SDS, BMI-SDS, insulin-like growth factor 1 (IGF-1)-SDS, and testosterone levels were significantly decreased.ConclusionsVitamin D deficiency and osteoporosis are common in pediatric IBD patients. As disease severity deteriorates, weight-SDS, IGF-1-SDS, and testosterone levels were decreased. Optimal pubertal development is necessary for bone health.

Fracture Risk Reduction by Bisphosphonates in Mastocytosis?

Fragility fractures (FFxs) and osteoporosis are frequent manifestations of indolent systemic mastocytosis (ISM). So far, the effect of antiosteoporotic therapy on FFxs has scarcely been investigated. This study evaluates the long-term effect of bisphosphonate treatment on FFxs, bone mineral density (BMD), and bone resorption in patients with ISM in daily clinical practice. Patients with ISM who received bisphosphonates because of osteoporosis and/or FFxs were retrospectively analyzed (n= 58). Fractures were recorded by vertebral fracture assessment, X-rays of the thoracolumbar spine, medical records, and a questionnaire. Five-year analysis (n= 30) was made by comparing observed 5-year FFx risk with MastFx-predicted FFx risk for patients with ISM not treated with antiosteoporotic drugs and analyzing 5-year change in BMD and serum collagen C telopeptide (sCTx) Z-scores. During the median follow-up of 7.3 years, 14 of 58 patients suffered 40 FFxs. Five- and 10-year FFx-free survival were 81.9% (standard error [SE], 5.5%) and 67.0% (SE, 7.7%), respectively. FFx risk was significantly higher in patients with previous vertebral FFxs (P= .004), lower femoral BMD at baseline (P= .042), and history of anaphylaxis (P= .028). No 5-year FFx risk reduction could be proven, possibly due to the small sample size. The lumbar BMD Z-score significantly increased from median (interquartile range [IQR])-2.20 (-2.80 to-1.50) to-1.50 (-2.30 to-0.60) (P < .001, n= 27). The sCTx Z-score decreased from median 0.71 (IQR,-0.59 to 2.39) to-0.95 (-1.30 to-0.16) (P= .008, n= 15). Bisphosphonates significantly increase BMD and decrease sCTx in patients with ISM. However, FFxs still frequently occur. Especially patients with previous FFxs remain at high risk of new FFxs.

Impaired skeletal health in patients with chronic atrophic gastritis

Objective: In chronic atrophic gastritis (CAG), destruction of gastric parietal cells causes anacidity and hypergastrinemia. Use of proton pump inhibitors, which also induces gastric anacidity, is associated with increased fracture rates. Our objectives were to study possible differences in bone mineral density (BMD) and bone quality in patients with CAG compared to controls.Material and methods: We performed a cross-sectional study on 17 CAG patients aged 54 ± 13 years and 41 sex- and age-matched controls. Lumbar and femoral BMD and bone quality assessed by lumbar trabecular bone score (TBS) were measured by DXA, and bone material strength (BMS) by microindentation of the tibia. Serum bone markers (CTX, P1NP, sclerostin, osteocalcin, OPG, RANKL) were analyzed.Results: We found lower lumbar BMD Z-score (−0.324 ± 1.096 versus 0.456 ± 1.262, p = 0.030), as well as a higher frequency of osteoporosis at the lumbar spine (p = 0.046) and osteopenia at total hip (p = 0.019) in patients compared to controls. In a post hoc subgroup analysis, we observed that the differences were confined to the male patients. TBS also tended to be lower in male patients (p = 0.059), while BMS did not differ between the groups. Osteocalcin, sclerostin, OPG, and OPG/RANKL ratio were lower in patients compared to controls, while CTX and P1NP did not differ between the groups.Conclusions: We observed lower lumbar BMD, increased frequency of osteopenia and osteoporosis in male, but not female patients with CAG. Bone markers suggest a decrease in bone formation and increased bone resorption in CAG patients compared to controls.

Biochemical markers of bone turnover in children with clinical bone fragility.

The role of biochemical bone turnover markers (BTMs) in assessing low bone mass and monitoring bisphosphonate treatment in pediatric patients with clinical bone fragility is not well established. The aim of the study was to examine the correlations of BTMs and the bone mineral density (BMD), and evaluate the effects of bisphosphonates therapy on BTMs in children with clinical bone fragility. Clinical data of 115 patients with clinical bone fragility (mean age 9.7±5.8 years), 102 of whom received bisphosphonates, were studied. Serum alkaline phosphatase (ALP), osteocalcin (OC), urine pyridinoline (PD) and deoxypyridinoline (DPD), BMD at baseline and subsequent years were analyzed. There was a significant negative correlation between urine PD and lumbar BMD (slope=-0.29, p<0.001). There were no correlations between BTMs and lumbar BMD Z-score. There was a significant positive correlation between serum OC and serum ALP, urine PD and DPD (p<0.001). Serum OC, urine PD and DPD index, as expressed as measured value/upper limit of normal value for age, decreased during the first 3 years of bisphosphonate therapy. In children with clinical bone fragility, BTMs correlated with each other, but not with lumbar BMD Z-score. While they were not reliable predictors of degree of low BMD, the bone markers showed suppression during bisphosphonate therapy and may be helpful in monitoring the response to therapy.

Bone Microarchitecture Is Impaired in Adolescent Amenorrheic Athletes Compared with Eumenorrheic Athletes and Nonathletic Controls

Bone mineral density (BMD) is lower in young amenorrheic athletes (AA) compared to eumenorrheic athletes (EA) and nonathletic controls and may contribute to fracture risk during a critical time of bone accrual. Abnormal bone microarchitecture is an independent determinant of fracture risk and has not been assessed in young athletes and nonathletes. We hypothesized that bone microarchitecture is impaired in AA compared to EA and nonathletes despite weight-bearing exercise. We conducted this cross-sectional study at the Clinical Research Center of Massachusetts General Hospital. We assessed BMD and bone microarchitecture in 50 subjects [16 AA, 18 EA, and 16 nonathletes (15-21 yr old)] using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Groups did not differ for chronological age, bone age, body mass index, or vitamin D levels. Lumbar BMD Z-scores were lower in AA vs. EA and nonathletes; hip and femoral neck BMD Z-scores were highest in EA. At the weight-bearing tibia, athletes had greater total area, trabecular area, and cortical perimeter than nonathletes, whereas cortical area and thickness trended lower in AA. Trabecular number was lower and trabecular separation higher in AA vs. EA and nonathletes. At the non-weight-bearing radius, trabecular density was lower in AA vs. EA and nonathletes. Later menarchal age was an important determinant of impaired microarchitecture. After controlling for covariates, subject grouping accounted for 18-24% of the variability in tibial trabecular number and separation. In addition to low BMD, AA have impaired bone microarchitecture compared with EA and nonathletes. These are the first data to show abnormal bone microarchitecture in AA.

1382 ARE CHILDREN WITH STONES AT RISK FOR BREAKING BONES? BONE MINERAL DENSITY ANALYSIS IN PEDIATRIC STONE FORMERS

You have accessJournal of UrologyPediatrics: Stone Disease & Tumors1 Apr 20111382 ARE CHILDREN WITH STONES AT RISK FOR BREAKING BONES? BONE MINERAL DENSITY ANALYSIS IN PEDIATRIC STONE FORMERS Candace Granberg, Katherine Twombley, Aditya Bagrodia, Khashayar Sakhaee, Naim Maalouf, Linda A. Baker, and Nicol C. Bush Candace GranbergCandace Granberg Dallas, TX More articles by this author , Katherine TwombleyKatherine Twombley Dallas, TX More articles by this author , Aditya BagrodiaAditya Bagrodia Dallas, TX More articles by this author , Khashayar SakhaeeKhashayar Sakhaee Dallas, TX More articles by this author , Naim MaaloufNaim Maalouf Dallas, TX More articles by this author , Linda A. BakerLinda A. Baker Dallas, TX More articles by this author , and Nicol C. BushNicol C. Bush Dallas, TX More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1227AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Adult stone formers are known to have lower bone mineral density (BMD) and higher rates of osteoporotic fractures compared to non-stone formers. Low BMD in children is associated with increased risk of bone fractures. The objective of this study was to evaluate BMD among our pediatric stone patients. METHODS Retrospective review of all patients undergoing dual-energy x-ray absorptiometry (DXA) scan since 2000 with a confirmed diagnosis of urolithiasis was performed. Immobilized patients were excluded. Z-scores, expressed as number of age- and gender-matched standard deviations from the mean, and 24-hour urine profiles were assessed. Since 2009, patients with ≥ 1 stone have been prospectively queried about fracture history. Hypercalciuria was defined as Ca/Cr ratio > 0.2 and/or > 4 mg/kg/day. Statistical testing was performed with Fisher's exact and t-test, with p<0.05 considered statistically significant. RESULTS 132 confirmed stone-formers (76F:56M) underwent DXA analysis at average age 12.2 years. Average lumbar and radial forearm BMD Z-scores were −0.8 (range −4.2 to +2.7) and −0.5 (range −2.9 to +2.2), respectively. Lumbar BMD Z-scores were < −1.0 in 51/127 (40.2%) patients, and < −2.0 in 21/127 (16.5%). 79 of 132 children have completed 24-hour urine stone risk analysis, demonstrating 45.6% with hypercalciuria. Table 1 stratifies BMD Z-score based on presence or absence of hypercalciuria. Hypercalciuria was not associated with risk of BMD Z-score < −1 (p=0.36). Among 22 stone-formers who were prospectively queried about bone fracture history, 7 (31.8%) had one or more fractures. Average BMD Z-score in those with versus without fractures was −1.1 and −0.7, respectively. Table 1. DXA results based on presence or absence of hypercalciuria. Non-hypercalciuric Hypercalciuric p-value Total patients (n=79) 43(54.4%) 36(45.6%) Mean lumbar Z-score(SD) −0.9(1.08) −1.0(1.83) 0.76 Z-score < -1, n(%) 22(51.2) 14(38.9) 0.36 Z-score < -2, n(%) 9(20.9) 7(19.4) 1.00 Mean radial Z-score(SD) −0.2(1.35) −0.8(1.46) 0 CONCLUSIONS Pediatric stone disease may identify an at-risk population for future osteoporosis and fractures. Over 40% of our pediatric stone formers had Z-scores < −1.0, a value associated with increased fracture risk in children. Screening DXA scans should be performed in pediatric stone-formers and/or hypercalciurics, particularly in those with a history of fracture. Since adolescence is the period for peak bone mass accrual, it may be the ideal time for dietary and/or medical intervention to decrease future osteoporotic risk. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e551 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Candace Granberg Dallas, TX More articles by this author Katherine Twombley Dallas, TX More articles by this author Aditya Bagrodia Dallas, TX More articles by this author Khashayar Sakhaee Dallas, TX More articles by this author Naim Maalouf Dallas, TX More articles by this author Linda A. Baker Dallas, TX More articles by this author Nicol C. Bush Dallas, TX More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Comparative study of dual energy X‐ray absorptiometry and quantitative ultrasonography with the use of biochemical markers of bone turnover in boys with haemophilia

Our aim was to evaluate bone status in boys with haemophilia using dual energy X-ray absorptiometry (DXA) and quantitative ultraSonography (QUS), and in addition, to compare these two methods with the use of biochemical markers of bone turnover. Twenty-six boys with a mean decimal age of 12.08 ± 4.44 years were included in the study which included a DXA scan at lumbar spine and radial, as well as tibial QUS. Serum levels of soluble receptor activator of nuclear factor κB ligand (sRANK-L), osteoprotegerin (OPG) and osteocalcin (OC) were measured and joint evaluation was performed using the Hemophilia Joint Health Score (HJHS). With regard to the study results, only 2 of 26 patients (7.7%) had bone mineral density (BMD) Z-scores < -2, and 4 patients (15.4%) had BMD Z-scores between -1 and -2. Only one patient had radial and other two had tibial QUS Z-scores < -2. No agreement was recorded between QUS and DXA in identifying patients at risk for osteoporosis (k = 0.275, P = 0.063). Haemophiliacs had significantly higher serum levels of sRANK-L (21.04 ± 4.78 vs. 18.58 ± 2.28 ng mL(-1), P = 0.038) and of OC (5.35 ± 2.29 vs. 3.09 ± 0.61 ng mL(-1), P = 0.002) and significantly decreased levels of OPG (15.78 ± 2.53 vs. 23.79 ± 4.39 pg mL(-1), P < 0.001) compared with controls. QUS Z-scores at tibia significantly correlated with HJH Scores (r = -0.450, P = 0.040), whereas lumbar BMD Z-scores significantly correlated with body mass index Z-scores (r = 0.500, P = 0.009). More studies are warranted to identify the most accurate densitometric method for assessing bone status in haemophiliacs.

Bone mineral density and bone turnover in Romanian children and young adults with classical 21‐hydroxylase deficiency are influenced by glucocorticoid replacement therapy

It remains controversial if glucocorticoid replacement therapy impairs bone mineral density (BMD) in young patients with 21-hydroxylase deficiency. We aimed to analyze the impact of treatment variables, phenotype and genotype on BMD and bone metabolism in these patients. Cross-sectional study. Twenty-eight Caucasian patients with classical 21-hydroxylase deficiency (5-39 years). Clinical parameters, hormonal status, osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), genotype and lumbar BMD (Z-scores) were assessed. Cumulative and mean hydrocortisone equivalent doses were calculated for the entire treatment period. Patients with severely reduced BMD Z-scores (< or = -2.5 SD) had significantly higher mean/cumulative glucocorticoid doses compared to patients with moderately reduced (P = 0.003/P = 0.026) and normal Z-scores (> -1 SD) (P = 0.005/P = 0.011). Mean hydrocortisone equivalent doses > 20 mg/m(2)/day led to significantly lower lumbar BMD Z-scores (-2.16 +/- 1.4 SD) vs. doses </= 20 mg/m(2)/day (-0.59 +/- 1.25 SD) (P = 0.008). BMD correlated negatively with mean/cumulative glucocorticoid doses and treatment duration. OC (86.45 +/- 37.45 ng/ml) and CTX (1.45 +/- 0.43 ng/ml) were significantly increased compared to an age- and sex-matched control group in patients with active growth; only CTX was slightly increased in patients who completed growth. High cumulative and mean glucocorticoid doses negatively impact on BMD in children and young adults with classical 21-hydroxylase deficiency. Substitution therapy should be adapted particularly at this life period to prevent bone loss.

Prospective Study of Changes in Bone Mineral Density and Turnover in Children after Hematopoietic Cell Transplantation

Osteoporosis is common in adults after hematopoietic cell transplantation (HCT). The data on bone mineral density (BMD) in children after HCT are limited. The objective of the study was to determine the incidence, timing, magnitude, and possible predictors of bone loss in children after HCT. The study population included 49 patients (age 5-18 yr) who were eligible to receive HCT at the University of Minnesota. The patients were evaluated at baseline, 100 d, 6 months, and 1 yr after HCT. Lumbar BMD (LBMD) was assessed by dual-energy x-ray absorptiometry. The number of patients with osteopenia increased from 18% at baseline to 33% 1 yr after HCT, and with osteoporosis from 16-19%. Mean areal LBMD z-score decreased from -0.56 to -1.1 by 6 months (n = 27) and at 1 yr was -0.94 (n = 21), which was significant compared with standard normal distribution (P = 0.004 and P = 0.022, respectively). The absolute loss of bone mineral corresponded to a 5.3% reduction in areal LBMD and a 4.8% reduction in volumetric LBMD. The level of bone-specific alkaline phosphatase decreased by 30% by d 100 (P = 0.009), followed by recovery toward baseline by 6 months. The level of osteocalcin greater than 6.5 ng/ml at d 100 predicted recovery from the initial bone loss by 1 yr. A reduction in LBMD at 6 months correlated with a cumulative dose of glucocorticoids. This study demonstrates that bone loss is common in children after HCT and is primarily due to suppression of bone formation. Further studies are necessary to validate osteocalcin as a predictive biomarker.

Serum zinc and its relation to bone mineral density in beta-thalassemic adolescents.

Trace elements have been considered to play critical roles in bone metabolism. This study aims at determining the serum zinc profile and its association with bone mineral density (BMD) abnormalities in thalassemic patients. In 131 transfusion-dependent beta-thalassemic patients, aged 10-20 yr, serum levels of zinc were measured by flame atomic absorption spectrophotometry (F-AAS). BMD values at the lumbar (L1-L4) and femoral neck were determined by dual X-ray absorptiometry (DXA). Dietary zinc intake and daily consumption of calcium were evaluated by a food-frequency questionnaire. Low serum zinc was found in 84.8% (in 44.7% severely low). Below -2 BMD Z-scores were observed in 68.7% and 17.6% of the patients at the lumbar and femoral regions, respectively. Female patients with severe zinc deficiency had lower lumbar BMD Z-scores in comparison to the other females (-3.26 vs -2.54). Serum zinc in females with femoral BMD Z-scores < - 2 was significantly lower by 16.4 microg/dL than other females. Our study suggests that serum levels of zinc can be lowered in the thalassemic patients and partly affect the BMD.

Antithyroid therapy improves bony manifestations and bone metabolic markers in patients with Graves' thyrotoxicosis.

Abnormal bone metabolism in patients with Graves' thyrotoxicosis is well documented, but the precise time-course of its recovery remains poorly understood. The present study was undertaken to clarify longitudinal improvement in bony manifestations, especially in cortical bone, and bone metabolic markers in thyrotoxicosis. Two year prospective follow-up study in patients with Graves' disease. Ten consecutive patients with Graves' disease (seven males and three females, of mean (+/-SEM) age 39.3 +/- 3.9 years) were enrolled in the study and treated with antithyroid drugs. Thirteen sex- and age-matched patients with the disease in remission served as controls. Bony manifestations were evaluated both by fine cortical bone striations in the metacarpals on magnified roentgenograms and lumbar bone mineral density (BMD) measurement. Urinary deoxypyridinoline (dPYR) and serum pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) were monitored as markers of bone resorption, as well as serum osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP) and alkaline-phosphatase (ALP) as markers of bone formation. Initial elevated free thyroid hormone levels were normalized within a month of starting therapy. Striation indices of the metacarpals were 1.89 +/- 0.16 before therapy, higher than those of 0.49 +/- 0.12 in the controls (P < 0.0001); the indices gradually decreased to 1.00 +/- 0.20 (12 months) and 0.48 +/- 0.12 (24 months). Lumbar BMD Z-scores increased from -0.22 +/- 0.46 to 0.21 +/- 0.47 (12 months) and 0.68 +/- 0.48 (24 months) (P = 0.0029). Before therapy, urinary dPYR and serum ICTP concentrations were much higher than the control values (dPYR, +553%; ICTP, -396%, P < 0.0001), which declined promptly in the 2nd month. Serum OC, PICP and ALP were also significantly higher than in controls at first (OC, +287%; PICP, +225%; ALP, +196%), and remained elevated until 4 or 8 months. Bone resorption and cortical bone striations occur in untreated patients with Graves' thyrotoxicosis. The bone resorption rapidly ameliorates after normalization of thyroid hormone levels. In contrast, the accelerated bone formation persists for at least 4-8 months, suggesting positive uncoupling of bone remodelling. This dominant bone formation could result in the improvement in cortical bone striations and the increase in bone mineral density of trabecular bone.