MDCT-QCT, QUS, and DXA in healthy adults: An intermodality comparison.

Background: Cortical deceleration is the main reason for bone loss at peripheral sites. It was suggested that when peripheral bones were assessed for osteoporosis, management and therapy can be administered early. The main aim of this study was to assess the relationships between the central and peripheral measurements at different skeleton bone sites (spine, femur, forearm, tibia, and calcaneus) with available modalities: DXA, QUS, and MDCT-QCT. Methods: The volunteers recruited in this study did not have any history or evidence of metabolic bone disease. Blood test and DXA measurements were used as inclusion criteria to select 40 healthy participants. The selected volunteers underwent 3 imaging modalities: QCT, DXA, and QUS. DXA-based measurements were made on 3 sites, including spine, femur, and forearm. QCT and QUS measurements were done for distal of tibia and calcaneus bones, respectively. The extracted parameters from the 3 modalities were analyzed using a bivariate (Pearson) correlation (r) in statistical software. Results: The results showed moderate to good correlations between spongy bones in central and peripheral sites from all the modalities. However, there was no correlation between MDCT measures and central bone values. According to correlations between different peripheral sits, aBMD of 33% radius and trabecular vBMD in 38% distal tibia showed weak but significant relationship between peripheral bones (r=-0.342, p=0.044). Conclusion: The findings demonstrated how bones in central and peripheral sites were correlated. Multimodality imaging was used in this group of healthy volunteers. Also, it was found that QCT-based MDCT needs more optimization and requires further investigations.

Correlation between criteria of diagnosis of low bone mineral density in adult and pediatric thalassemic patients: a prospective study.

BACKGROUND: Finding the correlation between criteria for low bone mineral density (BMD) in adulthood and childhood is a matter of interest. This study aimed to find how many of thalassemic patients with Z-Score ≤-2 during childhood, will be found with T-Score ≤-2.5 or Z-Score ≤-2.0 in adulthood. METHODS: The results of BMDs (one in childhood and one in adulthood) of 30 patients with beta thalassemia major (12 males and 18 females) with mean age of 17.63 y/o in childhood and 20.67 y/o in adulthood were studied, retrospectively. A Norland XR-46 device was used for measuring BMD. RESULTS: Z-Score ≤-2 was found in 33% of children and T-Score ≤-2.5 and Z-Score ≤-2.0 was found in 43 and 66% of adults, respectively. Correlation of pediatric Z-scores was good with adult T-scores and Z-scores (0.699-0.833). Relation of low BMD diagnosis in pediatric and adults was significant, and Kappa showed a moderate to good correlation between criteria for low BMD in childhood and adulthood, both with special significance in femoral region (8.10-14.47 and 0.258-0.703, respectively). Z-score ≤-2 significantly increased risk of low BMD in adulthood only when T-Score ≤-2.5 was used as low BMD criteria in adulthood (6.2-15.7). More patients dropped to poorer diagnosis group when Z-Score ≤-2.0 was used as low BMD criteria in adulthood. CONCLUSIONS: There is a moderate to good agreement of these criteria, at least in femoral region but using T-Score ≤-2.5 as low BMD criteria in adulthood caused a better prediction power for Z-Score ≤-2 of childhood.

How Age, Sex and Transfusion Affects the Incidence of Endocrine and Bone Density Disorders in Major Thalassemic Patients.

Background: Beta-thalassemia major patients frequently have endocrinopathies. We tried to determine relation between demographic and transfusion factor and endocrinopathies. Methods: Major beta-thalassemia patients (n=114 cases), 3-38 yr of age, entered this study. Female to male ratio was 51/63. Children (less than 20 yr) formed 57% of participants. Information about bone mineral density (BMD) and hormonal and biochemistry blood evaluation including fasting blood sugar (FBS), ferritin, triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), testosterone (males), and estradiol (females) entered data sheet. Results: Sex and ferritin level showed no significant correlation with above disorders. Age significantly correlated to short stature, diabetes, low BMD at femur and neck (P, 0.031, 0.008, 0.009 and <0.001, respectively) . The risk of short stature had increased in 12 yr and older patients 7.71 times than younger patients (P= 0.008). The risk of diabetes had increased in 35 yr and older patients 26.25 times than younger patients (P= 0.03). The risk of Z-score ≤ -2 in femoral region has increased in 19 yr and older patients 5.84 times than younger patients (P= 0.002). The risk of Z-score ≤ -2 in spinal region has increased in 14 yr and older patients 17 times than younger patients (P= 0.007). Conclusion: The main factor related with endocrinopathies was age. The correlation between age and short stature, diabetes and low BMD was positive. Therefore, we recommend early monitoring of thalassemia patients (in their late childhood and early teenage) for these complications.

QUS characteristics in Normal Population: a Mini Review and our experience.

Objectives: Quantitative ultrasound (QUS) is a bone densitometry method that is less expensive and more portable than DXA. It is also noninvasive. QUS parameters include speed of sound (SOS), broad band ultrasound attenuation (BUA), and stiffness index (SI). This study defined normal values of QUS parameters in Iranian men and women. Methods: QUS of heels measured in 258 Iranian men and women, aged 20-76 y/o. They were participants of Iranian Multicenter Osteoporosis study (IMOS), selected by randomized sampling. QUS device was an Achilles+ (GE-Lunar) device. Results: Percentiles of SI (2.5%, 50%, and 97.5%) determined. We found a good agreement between the Iranian reference values and western reference (used by device) value in defining normal and osteoporotic people (κ = 0.875). Conclusion: Results from this study suggest that QUS of the heel may be a good method for diagnosis of low bone mass in different regions.

Relationship between endocrine changes and bone markers in pediatric thalassemic patients after hematopoietic stem cell transplantation.

BACKGROUND: Beta thalassemia major and its treatment by hematopoietic stem cell transplantation can have deleterious effects on bone integrity and a main part of such effects is due to their deleterious effects on endocrine systems. So, we assessed the effects of endocrine changes during HSCT (Hematopoietic Stem Cell Transplantation) on growing bones of pediatric thalassemic patients. METHODS: Bone-specific alkaline phosphatase and osteocalcin (bone formation markers), N-terminal telopeptide (NTX, bone resorption marker), calcium (Ca), phosphorus (P), alkaline phosphatase (Alk ph), parathyroid hormone (PTH), vitamin D (vit D), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), insulin-like growth factor 1 (IGF-1), testosterone (in males) or estradiol (in females), measured in 20 major thalassemic patients with mean age of 10.8±3.9 years. Parameters at the baseline (before HSCT), and 1 month and 3 months after HSCT. RESULTS: After stem cell transplantation, changes of mean serum levels of NTX, osteocalcin, prolactin, LH, T4, IGF-1, testosterone (in males), Ca, Alk ph, PTH, and vit D were not significant, but bone specific Alk ph, P, T3, TSH, FSH and estradiol changed significantly (P=0.013, P=0.001, P=0.48, P=0.02, P=0.04 and P=0.001, respectively). After one month, there was a significant positive relationship between osteocalcine and T3 (p= 0.009). After 3 months, also, there was a significant positive relationship between osteocalcine and T3 and T4 as well as a negative one with IGF-1 (P<0.001, P<0.02 and P<0.03, respectively). CONCLUSIONS: Endocrine disorders do not appear to have an overall positive or negative effect on bone metabolism (anabolism or catabolism) in HSCT pediatric thalassemic patients in short term (three months).

The role of using different reference population in the prevalence of low BMD in the thalassemia patients.

PURPOSE: Prevalence of osteoporosis reported as high as 50% in thalassemia major patients. We compared bone density (BMD) of our patients with results of bone densitometry of participants of a national study, to find if BMD diagnosis is ethnicity sensitive or not. METHODS: In 177 adult beta thalassemia major patients and 490 normal subjects of 20-39 y/o range, dual-energy X-ray absorptiometry of the spine and femur performed. Normal subjects participated in Iranian Multi-center Osteoporosis Study (IMOS). Mean and standard deviation of normal ones achieved and Z-score of patients re-calculated based on normal Iranians. As BMD of normal participants and patients performed by devices of different brands, analyses done based on calculated standard BMD of all participants. RESULTS: BMD of patients was significantly lower than normal participants (P value <0.001). Frequency of Z-score ≤-2 found in 52% and 56% of patients in femur and spine regions, respectively. New Z-score of patients according to Iranian normal populations calculated. Frequency of this new Z-score ≤-2 found in 16% and 72% of patients in femur and spine regions, respectively. CONCLUSIONS: We think in secondary osteoporosis, may be other cut-off points, especially according to BMD of normal population of that geographical region are needed.

Correction to: The role of using different reference population in the prevalence of low BMD in the thalassemia patients.

[This corrects the article DOI: 10.1007/s40200-019-00455-6.].

Defining cut-off values for the diagnosis of osteoporosis in postmenopausal women by quantitative ultrasonography of the phalanx.

AIM: Quantitative ultrasound (QUS) of the phalanx is a non-invasive, inexpensive and portable method for bone assessment. We determined a cut off point for it in the diagnosis of osteoporosis. METHODS: In 180 postmenopausal women, dual-energy X-ray absorptiometry (DEXA) of the spine and femur and QUS of the phalanx were performed. Then, the optimum cut-off point for QUS was determined. RESULTS: Osteoporosis was found in 28.8% of women by DEXA (18.3% in L2-L4, 3.9-7.8% in different regions of the femur) and in 28.9% by QUS. Agreement of the methods (kappa value) was 0.317 for spine and 0.036-0.068 for femoral regions. Using receiver-operating characteristic (ROC) curves, we found T-score of -2.0 as the optimum cut-off point of QUS in diagnosing osteoporosis in the spine (sensitivity and specificity were 78.8% and 55.9%, respectively). We did not find a cut-off point for femoral regions because the 95% confidence interval of the area under the ROC curve contained the diagonal line (p = 0.150, 0.179 and 0.05 for femoral neck, trochanter and total femur, respectively). We defined -2.5 as the other T-score cut-off point under these different conditions; more specificity is needed. CONCLUSION: Agreement was weak to moderate between the two methods. Thus QUS of the phalanx is not a good replacement for DEXA in defining osteoporosis, but it may be used as a screening method.

Short-term Assessment of HSCT Effects on the Hypothalamus-Pituitary Axis in Pediatric Thalassemic Patients.

BACKGROUND: Beta thalassemia major (BTM) and its treatment by hematopoietic stem cell transplantation (HSCT) may have deleterious effects on the endocrine systems. We assessed endocrine complications of HSCT in pediatric patients for 3 months. METHODS: In 20 (6 female) pediatric major thalassemic patients (mean age of 10.8 ± 3.9 years old), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), T4, T3, thyroid-stimulating hormone (TSH), IGF-1, testosterone (in males) or estradiol (in females) were measured as a batch at the Endocrinology and Metabolism Research Center (EMRC) of Tehran University of Medical Sciences (TUMS) laboratories before HSCT and 1 and 3 months afterwards. The cosyntropin test for all and the clonidine test for short stature patients was conducted before HSCT. RESULTS: Before HSCT, delayed puberty and hypogonadotropic hypogonadism was found in 10% and 20% of patients, respectively. GH deficiency, low IGF1 and short stature was found in 25%, 55% and 40% of patients, respectively. Hypocortisolism, hypothyroidism and panhypopituitarism was found in 15%, 10% and 15% of patients, respectively. Prevalence of hypogonadotropic hypogonadism, low IGF1, hypothyroidism and panhypopituitarism was found in 20%, 40%, 10% and 10% of patients after 3 months, respectively (delayed puberty and short stature prevalence do not change after 3 months). HSCT caused lower T3 and estradiol and higher TSH. Corticosteroid users (15) had higher GH and lower T3 and testosterone or estradiol. Ferritin had a significant (negative) correlation with (before) prolactin and a significant correlation with T3 and T4 after HSCT. Age and acute graft-versus-host disease (GVHD) had no significant effect. CONCLUSION: Considering the small sample size and short duration of the study, it is difficult to reach any conclusion however it seems HSCT does not appear to have an overall positive or negative effect on prevalence of pituitary- hypothalamus axis disorders in pediatric thalassemic patients in 3 months.

A novel modified electrode as GC/PPy-AuNPs-rGO/L-Cys/Ag@MUA nanostructure configuration for determination of CCP and CRP antibodies in human blood serum samples.

In this work, silver nanoparticles were synthesized and stabilized with 11-mercaptoundecanoateanions to produce a new Ag@MUA core shell structure, and its utilizing for fabrication of a new sensing film. Gold nanoparticles (AuNPs) were electrochemically produced and simultaneously immobilized into the electropolymerized polypyrrole (PPy) film with the reduced graphene oxide (rGO). The Ag@MUA was then grafted to the surface of GC/PPy-AuNPs-rGO film using L-cysteine (L-Cys) linker agent and trifluoromethanesulfonic anhydride (TF2O), at ambient temperature and under the electrode stirring. The characterization of the sensor was studied by scanning electron microscopy, electrochemical impedance spectroscopy, cyclic and square wave voltammetry techniques. The utility of the modified electrode for clinical diagnosis has been successfully demonstrated by the analysis of human blood serums with a certified CRP and CCP content. Thus, the proposed sensor shows simple preparation, accuracy and precision in the analysis of cytochrome c protein (CCP) and C-reactive protein (CRP (with less side interferences.

Comparison of bone mineral density changes in pediatric thalassemic patients with and without hematopoietic stem cell transplant.

OBJECTIVES: Beta thalassemia major is a genetic hemoglobin disorder that affects bone density. The disease leads to deteriorating bone structure but can be treated with hematopoietic stem cell transplant. We aimed to assess bone mineral density changes in pediatric beta thalassemia major patients who had undergone a hematopoietic stem cell transplant compared with similarly affected patients who had not undergone a hematopoietic stem cell transplant. MATERIALS AND METHODS: Forty beta thalassemia major patients, 20 transplant and 20 nontransplant, younger than 16 years of age were enrolled. The mean age of transplant patients was 8.15 years and nontransplant patients was 9.5 years (P = .242). The female:male ratio was 1:1 in both groups. None of the patients reached puberty during this study. Bone mineral density was evaluated in transplant patients before and 1 year after hematopoietic stem cell transplant. Bone mineral density of nontransplant patients also was evaluated 1 year after their initial bone mineral density test. A Norland XR-46 densitometer was used to make all bone mineral density measurements. None of the patients had a z score < -2. RESULTS: Mean bone mineral density changes in the femur and spine during this study were 0.008 ± 0.075 g/cm2 and 0.048 ± 0.045 g/cm2 in transplant patients and 0.045 ± 0.072 g/cm2 and 0.036 ± 0.058 g/cm2 in nontransplant patients. No significant differences between bone mineral density changes in transplant and nontransplant patients were detected during the study. CONCLUSIONS: No significant effects on bone mineral density were detected in hematopoietic stem cell transplant pediatric beta thalassemia major patients compared with similarly affected nontransplant patients. Studies of longer duration may be required to identify significant changes in bone mineral density in hematopoietic stem cell transplant patients.

Vitamin D deficiency and causative factors in the population of Tehran.

BACKGROUND: There are multiple studies in different countries regarding the prevalence of vitamin D deficiency. These studies showed high prevalence of vitamin D deficiency in Asian countries. This study tries to elucidate the prevalence of vitamin D deficiency and its influencing factors in population of Tehran. METHODS: 1210 subjects 20-64 years old were randomly selected. 25 (OH) D serum levels were measured. Duration of exposure to sunlight, the type of clothing and level of calcium intake and BMI were quantified based on a questionnaire. RESULTS: A high percentage of vitamin D deficiency was defined in the study population. Prevalence of severe, moderate and mild Vitamin D deficiency was 9.5%, 57.6% and 14.2% respectively. Vitamin D serum levels had no significant statistical relation with the duration of exposure to sunlight, kind of clothing and BMI. Calcium intake in the normal vitamin D group was significantly higher than the other groups (714.67 +/- 330.8 mg/day vs 503.39 +/- 303.1, 577.93 +/- 304.9,595.84 +/- 313.6). Vitamin D serum levels in young and middle aged females were significantly lower than the older group. CONCLUSIONS: Vitamin D deficiency has a high prevalence in Tehran. In order to avoid complications of vitamin D deficiency, supplemental dietary intake seems essential.

Relation between BMD and biochemical, transfusion and endocrinological parameters in pediatric thalassemic patients.

UNLABELLED: Low BMDs, short stature, hypogonadism, subclinical hypothyroidism, and IFG are found in 3.3, 10, 33, 16.6, 6.6, and 26.6 % of 30 pediatric ß thalassemia major patients, respectively. Age is related with low Z-scores. Short stature and hypogonadism patients were older. These patients' monitoring in late childhood and early teenage for these complications is recommended. BACKGROUND: Beta-thalassemia major patients frequently have low BMD and increased fracture risk. We tried to determine the relation between BMD and biochemical, transfusion, and endocrinological parameters in pediatric patients. METHODS: Thirty beta-thalassemia major patients entered the study. Male to female ratio was 14/16. Physicians collected demographic; anthropometric; menstrual; transfusion and treatments histories; and serum levels of calcium, phosphorus, alkalin phosphatase, FBS, Hb, Ferritin, T3, T4, TSH, LH, FSH, testosterone (for boys), and estradiol (for girls). BMD of the spine and femur was measured using a DXA Norland XR-46 device. RESULTS: Prevalence of "low bone density" (Z-score < -2) in the spine and femur was 3.3 and 10 %, respectively. Short stature (Z-score < -2.5) and hypogonadism was seen in 33 and 16.6 % of patients, respectively. Hypogonadism was found only in boys. Subclinical hypothyroidism and impaired fasting glucose were found in 6.6 and 26.6 % of our patients, respectively. Age and transfusion duration was positively related with spinal BMD (P values, <0.001 and <0.001, respectively), and both related negatively with spinal Z-score (P values, 0.014 and 0.043, respectively). Age and transfusion duration related positively with femoral BMD (P values 0.030 and 0.017, respectively), and both related negatively with femoral Z-score (P values, 0.015 and 0.041, respectively). Mean age of short stature and hypogonadism patients were significantly higher than those who were normal (P values, 0.007 and 0.044, respectively). CONCLUSION: The main factor related with lower Z-scores of the femur and spine was age. Short stature and hypogonadism patients were significantly older. So, we recommend early monitoring of thalassemia patients (in their late childhood and early teenage) for these complications.

Changes of bone density in pediatric patients with ß-thalassemia major after allogenic hematopoietic stem cell transplantation.

BACKGROUND: Thalassemia major and its treatment by stem cell transplantation can have deleterious effects on bone integrity. This study assesses the adverse effects of transplantation on growing bones of pediatric thalassemic patients. METHODS: Bone mineral density (BMD) of 20 patients from three thalassemia classes whose mean (SD) age was 7.4 (3.8) years were tested with a Norland XR-46 device at baseline (before transplantation), 6 and 12 months after transplantation. RESULTS: At 6 and 12 months after transplantation we observed no significant changes in mean BMD. There were no Z-scores less than -2 among patients. Class 3 thalassemia did not negatively impact BMD. Calcium (Ca), phosphorous (P) and ferritin levels were not significantly related to patients' BMD scores. Transfusion duration and chelation therapy showed positive significant relationships to BMD (g/cm(2)), but no significant relation with the BMD Z-score. The deleterious relation between corticosteroid use and changes in BMD was not significant. In contrast, patients who developed acute graft versus host disease (aGVHD) after transplantation showed significant adverse effects on BMD of their femur (P = 0.020) and spine (P = 0.027). CONCLUSION: Stem cell transplantation in pediatric thalassemic patients who do not develop aGVHD does not appear to have any significant positive or negative effects on BMD.

A case-control study on risk factors of osteoporosisin patients with Crohn's disease.

BACKGROUND: Osteoporosis has been frequently reported in patients with inflammatory bowel diseases, especially Crohn's disease. METHODS: All consecutive Crohn's disease patients who attended the GI Clinics at Shariati Hospital, Tehran, Iran, from 2004 to 2007 were evaluated. A BMD-DEXA assessment was performed for all patients. Among those patients diagnosed with osteoporosis (T score

Correlation of quantitative heel ultrasonography with central dual-energy X-ray absorptiometric bone mineral density in postmenopausal women.

OBJECTIVES: In this study, we sought the proper cutoff level for quantitative ultrasonography (QUS) of the heel in identifying bone mineral density (BMD) categories as determined by dual-energy x-ray absorptiometry (DXA) in postmenopausal women. METHODS: With the use of DXA, BMD categories of the lumbar spine and different areas of the left femur of 420 healthy women according to World Health Organization definitions were determined. Quantitative ultrasonography of the heel was also performed in each subject. Receiver operating characteristic curves were plotted, and sensitivity and specificity of QUS to diagnose osteoporosis were examined at different points to identify the best cutoff level. The diagnostic agreement between the two techniques in identifying osteoporosis was assessed with kappa scores. RESULTS: The kappa scores were 0.31 for the lumbar region and 0.5 for the femoral neck region. On the receiver operating characteristic study, a score of -1 was found to be the appropriate cutoff point for QUS studies, in which the sensitivity of QUS to diagnose BMD osteoporosis varied between 78% and 87.5% depending on the site of the DXA study. With the proposed cutoff point (-1), sensitivity and specificity of QUS in detecting osteoporosis at the lumbar spine were 83.9% and 51%, respectively, and at the femoral neck were 84% and 50%, respectively. CONCLUSIONS: Insufficient agreement between QUS and DXA led to uncertainty on expected BMD in people tested by QUS. The proposed cutoff value could achieve higher sensitivity but only by accepting higher rates of false-positive results.