Assessing Bone Quality Using Trabecular Bone Score in Patients with Hemoglobinopathies

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3629-3629
Author(s):  
Melissa Cervantes ◽  
Ashutosh Lal ◽  
Anne M Marsh ◽  
Ellen B. Fung
Keyword(s):  
Bone Mass ◽  
Bone Quality ◽  
Trabecular Bone Score ◽  
Iron Concentration ◽  
Healthy Controls ◽  
Low Bone Mass ◽  
Liver Iron Concentration ◽  
Mineral Density ◽  
Liver Iron ◽  
The Relationship

Abstract Introduction: Osteoporosis is characterized by a decrease in bone mass and density with enlarged trabecular space resulting in porosity and bone fragility. It has been described in as many as 70 to 80% of adults with thalassemia (Thal) and sickle cell disease (SCD). Though assessment by DXA scan is now part of routine clinical practice, bone quality has been poorly characterized, particularly in SCD. Trabecular bone score (TBS) is a new textural analysis of lumbar spine DXA scans that reflects bone microarchitecture, shown to be highly predictive of fracture in adults. The objectives of this study were 1) to determine the prevalence of poor bone quality as assessed by TBS in patients with Thal and SCD, compared to healthy individuals and 2) to assess the relationship between bone quality and clinical predictors (age, transfusion status, liver iron concentration, diet, BMI, endocrinopathies). Methods: A retrospective chart review was conducted in patients > 10 years and > 40 Kg with Thal or SCD who had a spine bone mineral density (BMD) scan performed in the previous 5 years. Patients had on average 1.7±0.9 spine scans during the collection period (range 1-5); all scans were reanalyzed using the TBS software (Insight, MediMaps v2.2, France). Optimal bone quality was defined as TBS >1.35; subnormal TBS= 1.34-1.20; abnormal <1.20. Liver iron concentration (LIC) was assessed by SQUID. Data from healthy controls without Thal or SCD were collected from previously completed research studies. Statistical analysis was performed using STATA, v. 9.0 (College Station, TX). This study was approved by the Institutional Review Board at UCSF Benioff Children's Hospital Oakland. Results: Data from 251 patients were abstracted which included, 162 females, 173 adults; 81 Thal, 102 SCD, and 68 healthy controls. Thal patients were older than SCD or controls (29.7 vs. 23.8, 25.8 years, p<0.05) and had lower LIC (2303 vs. 3014 µg Fe/g wet wt., p=0.004) but higher incidence of hypogonadism (31% vs. 1%, p<0.001). No differences were observed in vitamin D status, fracture history or family history of osteoporosis. On average, Thal patients had greater deficits in spine BMD Z-score (-2.1±1.2, Mean±SD), as compared to SCD (-1.0±1.5) and controls (-0.1±0.8), as well as a higher prevalence of abnormal bone quality by TBS (29.7%) vs. 12.2% in SCD, 4.6% in control, (p<0.001). TBS was positively correlated with BMD (r=0.7, p<0.001) and negatively correlated with age (r=-0.28, p<0.001). After controlling for age, BMI, hypogonadism and diagnosis, LIC was negatively associated with bone quality (r=0.30, p=0.001). Conclusions: These data support the relationship between reduced bone mass and bone quality in adult and adolescent patients with hemoglobinopathies. Older patients with low bone mass appear to be at particular risk for abnormal bone quality. TBS may be a valuable clinical tool in the assessment of true fracture risk in this group of patients with extremely low bone mineral density. However, future research is needed to develop models that include BMD and TBS for prediction of absolute fracture risk and need for treatment of low bone mass in patients with hemoglobinopathies. Disclosures No relevant conflicts of interest to declare.

In-Accuracy Of Bone Density Measurements By DXA In Patients With Hemoglobinopathies and Iron Overload

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 966-966
Author(s):  
Haven M. Allard ◽  
Marcela G. Weyhmiller ◽  
Ashutosh Lal ◽  
Ellen B. Fung
Keyword(s):  
Lumbar Spine ◽  
Iron Content ◽  
Iron Concentration ◽  
Lumbar Vertebrae ◽  
Healthy Controls ◽  
Z Score ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Liver Iron Content ◽  
Z Scores

Abstract Introduction When monitoring bone health in patients with hemoglobinapathies, it is unknown if iron in surrounding tissues can lead to inaccuracies in the 2-dimensional assessment by Dual Energy X-ray Absorptiometry (DXA). Objective The aims of this study were: 1) to determine if the accuracy of lumbar spine assessment by DXA is affected by high liver iron concentration in patients with Sickle Cell Disease (SCD) or Thalassemia (Thal), 2) to test the effect of high tissue iron on vertebral Z-scores using phantoms, 3) to explore the ability to account for potential high-iron content effects when performing DXA examinations. Methods This study consisted of a retrospective chart review of data collected by the Children’s Hospital & Research Center Oakland, Bone Density Clinic and Iron Measurement Program. Data from both DXA and Super Conducting Quantum Interference Device (SQUID) examinations collected between 2002 and 2013 from were abstracted. Only those patients with a diagnosis of SCD or Thal, who had a DXA and SQUID measurement within the same year were divided into an iron overload group (liver iron concentration (LIC) >3,000 µg Fe/g wet) and low iron (LIC <500 µg Fe/g wet) group. These patients were compared with healthy controls of which only 13 had both DXA and SQUID tests, 34 had DXA only. The 34 healthy controls without a SQUID test were included because it was assumed, based on their health screen that their liver-iron content would not interfere with DXA. In order to explore aim 1, a lumbar spine scan, by DXA, of each subject was re-analyzed to compare the derived areal bone mineral density (aBMD) Z-scores of lumbar vertebrae that are covered by the liver (presumed L1 or L1/L2) with the Z-scores of the lumbar vertebrae not covered by the liver (L3/L4). To explore aim 2, phantoms were designed to mimic the geometry of iron loaded tissues in order to explore the contribution of iron in specific tissues on the accuracy of DXA assessments. Phantoms were constructed using KNOX® brand gelatin and iron(II) sulfate heptahydrate and had concentrations ranging from 3,000 to 7,000 ug Fe/g gelatin. The iron-loaded phantoms were positioned obtusely overlying L1/L2 of the DXA daily quality control phantom to mimic the position of the liver. All data were analyzed by STATA ver.9.2 and were considered significant with a p<0.05. Results Data from 102 total visits abstracted from 88 subjects [19 SCD (13 F), 24 Thal (12 F), age: 30.1 ± 11.9 years, mean ± SD], and 45 healthy controls (24 F, age: 25.4 ± 11.0 yrs) were analyzed. The SCD and Thal group had an average LIC by SQUID of 4651 ± 2079 µg Fe/g wet tissue and serum ferritin of 5408±2706 ng/mL; while the healthy controls, with both a DXA and a SQUID (n=17), had an average LIC of 251±144. Average aBMD Z-score of the lumbar spine L1-L4 in the Thal group was -2.0 ± 1.1 , the SCD was -2.0 ± 1.6 and the healthy controls: -0.3 ± 0.9. However, when individual vertebrae are analyzed separately, a significant difference was observed between the lumbar spine L1 BMD Z-scores compared to the combined means of L3/L4 Z-scores in the iron loaded population (Table 1). The discrepancy was even greater in subjects with LIC >5000 ug/g wet tissue. These findings were reproduced using heavily iron loaded phantoms. Conclusions Initial results for this study show that there is a relationship between liver iron content and lumbar spine aBMD Z-scores when evaluated by DXA. The BMD Z-score for L1 appears to be more significantly affected by the liver iron content then L2, which was unanticipated. When evaluating patients with liver iron content >3,000 ug/g wet tissue, it is important to consider the effects of iron contribution from the liver on the DXA spine scans and delete L1 and/or L2 from the total Z-score prior to making an interpretation. Failing to do so may under diagnose low bone mass in this at risk patient population. Disclosures: No relevant conflicts of interest to declare.

Calibration of Improved T2* Method for the Estimation of Liver Iron Concentration in Transfusional Iron Overload.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2004-2004 ◽  
Author(s):  
Maciej W Garbowski ◽  
John-Paul Carpenter ◽  
Gillian Smith ◽  
Dudley J Pennell ◽  
John B Porter
Keyword(s):  
Liver Biopsy ◽  
Iron Concentration ◽  
Cardiovascular Imaging ◽  
Breath Hold ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Single Breath ◽  
Single Breath Hold ◽  
Tissue Iron ◽  
The Relationship

Abstract Abstract 2004 Poster Board I-1026 Background and rationale Non-invasive estimation of tissue iron concentration is being used increasingly to follow responses to chelation therapy. Magnetic resonance (MR) T2* was originally developed to estimate myocardial iron but the first description of the myocardial T2* method also demonstrated a clear relationship between liver T2* and liver iron concentration (LIC) measured by biopsy (Anderson, Eur Heart J 2001). The inclusion of liver analysis at this time was intended mainly to show the relationship of T2* to tissue iron rather than as a standard method for LIC measurement, particularly as the echo times used were too long to measure the high iron levels commonly found in the liver. Since this work, other MR methods such as the R2 technique (St. Pierre, Blood 2004) have been specifically validated to measure LIC. However, if T2* could be validated and calibrated appropriately for LIC, it may be convenient to measure liver and heart iron at the same time using this rapid technique. Since the initial calibration of the T2* method, there have been major improvements in scanner technology and hardware. In the original paper, eight different echo times were acquired (TE 2.2- 20.1ms), each of which required a separate breath-hold with important implications for image registration regarding the measurement of T2*. Much shorter, more closely spaced echo times are now possible in a single breath-hold which makes the calculation of T2* more accurate, especially at higher liver iron concentrations where T2* is short. Methods: A large cohort of patients at UCLH have had liver biopsies as part of iron chelation studies on Deferasirox, while continuing to be monitored by T2* of both heart and liver. Data pairs for LIC calibration curve plots were chosen as nested values by shortest biopsy-to-MR time lapse criterion (±75 days) from all biopsy and hepatic T2* results. Liver biopsy iron was measured in a single central laboratory in Rennes, France (Clinique des Maladies du Foie [Clinic for Hepatic Illnesses], Center Hospitalier Universitaire) on paraffin embedded sections as previously described (Soriano-Cubells MJ, Atomic Spectrosc. 1984). All MR scans were performed on a 1.5T Sonata MR scanner (Siemens, Germany) using a 4-channel anterior phased array coil at Royal Brompton Hospital, London. A transverse slice through the centre of the liver was imaged using a multi-echo single breath-hold gradient echo T2* sequence with a range of echo times (TE 0.93-16.0ms). T2* decay was measured using Thalassaemia tools (Cardiovascular Imaging Solutions, London, UK) from a region of interest (ROI) in an area of homogeneous liver tissue, avoiding blood vessels and other sources of artefact. To account for background noise, a truncation method was used for curve-fitting (He, Magn Reson Med 2008). All T2* measurements were performed in triplicate by 2 independent observers choosing three separate ROIs to analyse. The ROIs were chosen to be as large as possible in three separate areas of the liver (anterior, mid/lateral and posterior). Spearman correlation method was used to estimate the degree of relationship between biopsy LIC and hepatic R2* (1/T2*) values, both of which showed positive skew. Results and conclusions: 61 patients had both liver biopsy and liver MR measurements undertaken. However, only 18 had biopsies within 75 days of MR T2* measurement and these are the patients included in the following analysis. There is a linear relationship between biopsy LIC and the reciprocal of T2* (R2*), given by: LIC = 0.03 x R2* + 0.74 (R2=0.96 p<0.0001, slope 95% CI 0.027-0.033, with y intercept CI -0.73 to 2.2). The 95% confidence intervals for the linear regression line were calculated from the SEM and are shown as the broken lines (Figure 1). Staging of fibrosis/cirrhosis provided in biopsy reports was not found to significantly affect regression analysis contrary to previous studies. The inset shows the relationship between T2* and biopsy LIC. The new calibration shows acceptable linearity and reproducibility over an LIC range up to 30mg/g dry weight and gives LIC values approximately 1.94 times higher than the original method reported by Anderson. Comparison of these values with those obtained by SQUID and Ferriscan would also be of interest. Disclosures: Pennell: Cardiovascular Imaging SOlutions, London, UK: Director.

Serum Ferritin and Liver Iron Concentration in Patients with Iron Overload.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3833-3833
Author(s):  
Zahra Pakbaz ◽  
Roland Fischer ◽  
Ellen Fung ◽  
Peter Nielsen ◽  
Rainer Engelhardt ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Iron Concentration ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Transfusion Therapy ◽  
Poor Predictor ◽  
The Individual ◽  
The Relationship

Abstract Despite its limitations, serum ferritin (SF) is commonly used to monitor chelation therapy in primary and secondary hemochromatosis. To better predict liver iron concentration (LIC), we prospectively investigated the relationship between SF and LIC in a total of 421 patients with primary (HFE-1 associated, n=241) or secondary hemochromatosis (n=180), consisting of chronically transfused thalassemia (Tx-Thal: n=89) or sickle cell disease patients (Tx-SCD: n=45) and transfusion independent thalassemia patients (nTx-Thal: n=26). In all patients, LIC was measured by SQUID biosusceptometry. SF correlated with LIC (RS = 0.51–0.83, p &lt; 0.001) but was a poor predictor for LIC. SF was significantly lower (p &lt; 0.001) in nTx-Thal and HFE-1 patients despite similar LIC (421 – 5524 μg/g-liver) and it was higher in Tx-SCD compared to Tx-Thal (p = 0.03). In order to improve the value of SF, we calculated the SF/LIC ratio for each group. SF/LIC remained stable over time in patients whose therapy did not change. In iron loaded patients without blood transfusion therapy (nTx-Thal and HFE-1), the median SF/LIC ratio was significant lower (0.32 and 0.43) as compared to transfused patients (Tx-Thal: 0.87, HCV-Thal: 0.99, Tx-SCD: 1.2), probably, indicating differences in the secretion of ferritin into plasma. We conclude that SF alone can mislead the iron unloading therapy as it underestimates LIC in nTx-Thal patients and overestimates LIC in Tx-SCD patients. Once the initial LIC value is obtained and the individual SF/LIC ratio is determined in a patient, the ratio together with SF may be more useful than SF alone to monitor iron overload and predict LIC.

scholarly journals Assessment of bone quality with trabecular bone score in patients with inflammatory bowel disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iulia Soare ◽  
Anca Sirbu ◽  
Sorina Martin ◽  
Mircea Diculescu ◽  
Bogdan Mateescu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Trabecular Bone ◽  
Bone Quality ◽  
Bowel Disease ◽  
Trabecular Bone Score ◽  
Study Cohort ◽  
Healthy Controls ◽  
Mineral Density ◽  
Lower Lumbar Spine ◽  
Inflammatory Bowel

AbstractInflammatory bowel disease (IBD) patients have a significant risk of developing bone loss. The trabecular bone score (TBS) is a relatively new parameter used to provide information on bone quality. The study cohort included 81 patients with IBD and 81 healthy controls. Blood tests, dual-energy x-ray absorptiometry (DXA), including TBS, were assessed. Harvey–Bradshaw Index (HBI) for Crohn's disease (CD) and the Partial Mayo Score for ulcerative colitis (UC) were used for evaluation of clinical disease activity. Compared with the healthy controls, the IBD patients had lower lumbar spine (LS) bone mineral density (BMD) (1.06 ± 0.18 vs. 1.16 ± 0.15 g/cm2, p < 0.005), hip BMD (0.88 ± 0.13 vs. 0.97 ± 0.13 g/cm2, p < 0.005) and TBS (1.38 ± 0.1 vs. 1.43 ± 0.1, p < 0.005) values. The patients with stricturing CD had lower TBS (1.32 ± 0.13 vs. 1.40 ± 0.9, p = 0.03) and LS BMD (0.92 ± 0.19 vs. 1.07 ± 0.1, p = 0.01) values compared with those with non-stricturing CD. Multivariate regression model analysis identified HBI as independent factor associated with TBS. Our results support that all DXA parameters are lower in patients with IBD than in healthy patients. Moreover, TBS is a valuable tool for assessment of bone impairment in active CD.

scholarly journals The Association between Bone Mineral Density and Periodontal Disease in Middle-Aged Adults

2021 ◽  
Vol 18 (6) ◽  
pp. 3321
Author(s):  
Hsin-Hua Chou ◽  
Sao-Lun Lu ◽  
Sen-Te Wang ◽  
Ting-Hsuan Huang ◽  
Sam Li-Sheng Chen
Keyword(s):  
Bone Mineral Density ◽  
Young Adults ◽  
Bone Mass ◽  
Periodontal Disease ◽  
Bone Mineral ◽  
Intervention Program ◽  
Past History ◽  
Low Bone Mass ◽  
Mineral Density ◽  
Periodontal Index

The association between osteoporosis and periodontal disease (PD) has been revealed by previous studies, but there have been few studies on the association in younger adults. We enrolled a total of 7298 adults aged 40 to 44 who underwent PD screening between 2003 and 2008. Data on quantitative ultrasound for the measurement of bone mineral density (BMD) were collected for the diagnostic criteria of osteopenia and osteoporosis. The Community Periodontal Index (CPI) was measured for defining PD. A multiple logistic regression model was used to assess the effect of low bone mass on the risk of PD. Of 7298 enrollees, 31% had periodontal pockets >3 mm, 36.2% had osteopenia, and 2.1% had osteoporosis. The 39.8% of PD prevalence was high in adults with osteoporosis, followed by 33.3% in osteopenia. A negative association was found between BMD and CPI value (p < 0.0001). Low bone mass was associated with the risk of PD (adjusted OR: 1.13; 95% CI:1.02–1.26) after adjusting the confounding factors, including age, gender, education level, overweight, smoking status, past history of osteoporosis, and diabetes mellitus. An association between BMD and PD among young adults was found. An intervention program for the prevention of PD and osteoporosis could be considered starting in young adults.

Liver iron concentration and fibrosis in a cohort of transfusion-dependent patients on long-term desferrioxamine therapy

2005 ◽  
Vol 5 (7) ◽  
pp. 572-578 ◽  
Author(s):  
Vasili Berdoukas ◽  
Timothy Bohane ◽  
Vivienne Tobias ◽  
Keshani De Silva ◽  
Ian Fraser ◽  
...  
Keyword(s):  
Iron Concentration ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Desferrioxamine Therapy
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