Metabolomic Profiling in Patients with Heart Failure and Exercise Intolerance: Kynurenine as a Potential Biomarker.

Aims: Metabolic and structural perturbations in skeletal muscle have been found in patients with heart failure (HF) both with preserved (HFpEF) and reduced (HFrEF) ejection fraction in association with reduced muscle endurance (RME). We aimed in the current study to create phenotypes for patients with RME and HFpEF compared to RME HFrEF according to their metabolomic profiles and to test the potential of Kynurenine (Kyn) as a marker for RME. Methods: Altogether, 18 HFrEF, 17 HFpEF, and 20 healthy controls (HC) were prospectively included in the current study. The following tests were performed on all participants: isokinetic muscle function tests, echocardiography, spiroergometry, and varied blood tests. Liquid chromatography tandem mass spectrometry was used to quantify metabolites in serum. Results: Except for aromatic and branched amino acids (AA), patients with HF showed reduced AAs compared to HC. Further perturbations were elevated concentrations of Kyn and acylcarnitines (ACs) in HFpEF and HFrEF patients (p < 0.05). While patients with HFpEF and RME presented with reduced concentrations of ACs (long- and medium-chains), those with HFrEF and RME had distorted AAs metabolism (p < 0.05). With an area under the curve (AUC) of 0.83, Kyn shows potential as a marker in HF and RME (specificity 70%, sensitivity 83%). In a multiple regression model consisting of short-chain-ACs, spermine, ornithine, glutamate, and Kyn, the latest was an independent predictor for RME (95% CI: −13.01, −3.30, B: −8.2 per 1 µM increase, p = 0.001). Conclusions: RME in patients with HFpEF vs. HFrEF proved to have different metabolomic profiles suggesting varied pathophysiology. Kyn might be a promising biomarker for patients with HF and RME.

Atraumatic femoral head necrosis: a biomechanical, histological and radiological examination compared to primary hip osteoarthritis.

INTRODUCTION: Atraumatic necrosis of the femoral head (AFHN) is a common disease with an incidence of 5000-7000 middle-aged adults in Germany. There is no uniform consensus in the literature regarding the configuration of the bone in AFHN. The clinical picture of our patients varies from very hard bone, especially in idiopathic findings, and rather soft bone in cortisone-induced necrosis. A better understanding of the underlying process could be decisive for establishing a morphology-dependent approach. The aim of this study is the closer examination of the condition of the bone in the AFHN compared to the primary hip osteo arthritis (PHOA). MATERIALS AND METHODS: The preparations were obtained as part of elective endoprosthetic treatment of the hip joint. Immediately after sample collection, thin-slice CT of the preserved femoral heads was performed to determine the exact density of the bone in the necrosis zone. Reconstruction was done in 0.8-1 mm layers in two directions, coronary and axial, starting from the femoral neck axis. Density of the femoral heads was determined by grey value analysis. The value in Hounsfield units per sample head was averaged from three individual measurements to minimize fluctuations. For biomechanical and histomorphological evaluation, the samples were extracted in the load bearing zone perpendicular to the surface of the femoral head. Group-dependent statistical evaluation was performed using single factor variance analysis (ANOVA). RESULTS: A total of 41 patients with a mean age of 64.44 years were included. The mean bone density of the AFHN samples, at 1.432 g/cm3, was about 7% higher than in the PHOA group with a mean value of 1.350 g/cm3 (p = 0.040). The biomechanical testing in the AFHN group showed a 22% higher-but not significant-mean compressive strength (20.397 MPa) than in the PHOA group (16.733 MPa). On the basis of histological analysis, no differentiation between AFHN and PHOA samples was possible. CONCLUSIONS: The present study (NCT, evidence level II) shows that AFHN has a very well detectable higher bone density compared to PHOA. However, neither biomechanical stress tests nor histomorphological evaluation did show any significant difference between the groups. The results allow the conclusion that there is no "soft" necrosis at all in the AFHN group.

Psychosocial factors, mental health, and coordination capacity in patients with heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction.

AIMS: Patients with heart failure (HF) suffer from reduced quality-of-life (QoL). We aimed to compare QoL, depression, and anxiety scores among outpatients with preserved (HFpEF) and reduced (HFrEF) ejection fraction and non-HF controls and its relationship to coordination capacity. METHODS AND RESULTS: Fifty-five participants were recruited prospectively at the University Hospital Jena, Germany (17 HFpEF, 18 HFrEF, and 20 non-HF controls). All participants underwent echocardiography, cardiopulmonary exercise testing (CPET), 10 m walking test (10-MWT), isokinetic muscle function and coordination tests, and QoL assessments using the short form of health survey (SF-36), and hospital anxiety and depression scale (HADS). Furthermore, inflammatory biomarkers such as growth differentiation factor-15 (GDF-15) were assessed. Patients with HFpEF showed compared with HFrEF and non-HF controls reduced QoL [mental component score (MCS): 43.6 ± 7.1 vs. 50.2 ± 10.0 vs. 50.5 ± 5.0, P = 0.03), vitality (VT): 47.5 ± 8.4 vs. 53.6 ± 8.6 vs. 57.1 ± 5.2, P = 0.004), and elevated anxiety (6.5 ± 3.2 vs. 3.3 ± 2.8 vs. 3.8 ± 2. 8, P = 0.02) and depression scores (6.5 [3.5-10.0] vs. 3.0 [1.0-6.5] vs. 2.0 [0.75-3.0], P = 0.01)]. After adjusting to multiple comparisons, anxiety remained higher in HFpEF patients compared with HFrEF (ppost-hoc  = 0.009). HFpEF and HFrEF patients showed reduced coordination capacity compared with non-HF controls (P < 0.05). In a logistic regression, the presence of depression score ≥8 remained an independent factor for predicting reduced coordination capacity after adjusting for peak VO2 , GDF-15, 10-MWT, physical component score (PCS), and peak torque of the leg [odds ratio (OR): 0.1, 95% confidence interval (CI): 0.004-0.626, P = 0.02]. CONCLUSION: Outpatients with HFpEF had worse QoL and higher anxiety and depression scores compared with HFrEF and non-HF controls. Depression is associated with reduced QoL and is an independent predictor for reduced coordination capacity.

Skeletal Muscle Function, Structure, and Metabolism in Patients With Heart Failure With Reduced Ejection Fraction and Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Reduced exercise capacity in patients with heart failure (HF) could be partially explained by skeletal muscle dysfunction. We compared skeletal muscle function, structure, and metabolism among clinically stable outpatients with HF with preserved ejection fraction, HF with reduced ejection fraction, and healthy controls (HC). Furthermore, the molecular, metabolic, and clinical profile of patients with reduced muscle endurance was described. METHODS: Fifty-five participants were recruited prospectively at the University Hospital Jena (17 HF with preserved ejection fraction, 18 HF with reduced ejection fraction, and 20 HC). All participants underwent echocardiography, cardiopulmonary exercise testing, 6-minute walking test, isokinetic muscle function, and skeletal muscle biopsies. Expression levels of fatty acid oxidation, glucose metabolism, atrophy genes, and proteins as well as inflammatory biomarkers were assessed. Mitochondria were evaluated using electron microscopy. RESULTS: Patients with HF with preserved ejection fraction showed compared with HF with reduced ejection fraction and HC reduced muscle strength (eccentric extension: 13.3±5.0 versus 18.0±5.9 versus 17.9±5.1 Nm/kg, P=0.04), elevated levels of MSTN-2 (myostatin-2), FBXO-32 (F-box only protein 32 [Atrogin1]) gene and protein, and smaller mitochondrial size (P<0.05). Mitochondrial function and fatty acid and glucose metabolism were impaired in HF-patients compared with HC (P<0.05). In a multiple regression analysis, GDF-15 (growth and differentiation factor 15), CPT1B (carnitine palmitoyltransferase IB)-protein and oral anticoagulation were independent factors for predicting reduced muscle endurance after adjusting for age (log10 GDF-15 [pg/mL] [B, -54.3 (95% CI, -106 to -2.00), P=0.043], log10 CPT1B per fold increase [B, 49.3 (95% CI, 1.90-96.77), P=0.042]; oral anticoagulation present [B, 44.8 (95% CI, 27.90-61.78), P<0.001]). CONCLUSIONS: Patients with HF with preserved ejection fraction have worse muscle function and predominant muscle atrophy compared with those with HF with reduced ejection fraction and HC. Inflammatory biomarkers, fatty acid oxidation, and oral anticoagulation were independent factors for predicting reduced muscle endurance.

Bone matrix mineralization and osteocyte lacunae characteristics in patients with chronic kidney disease - mineral bone disorder (CKD-MBD).

OBJECTIVES: Little is known about bone mineralization and osteocyte lacunae properties in chronic kidney disease mineral bone disorder (CKD-MBD). METHODS: In this retrospective study, we measured the bone mineralization density distribution (BMDD) and osteocyte lacunar section (OLS) 2D-characteristics by quantitative backscatter electron imaging in Straumann drill biopsy samples from n=58 patients with CKD-MBD. Outcomes were studied in relation to serum parathyroid hormone (PTH), alkaline phosphatase (APH), histomorphometric bone turnover and treatment with cinacalcet or phosphate binders. RESULTS: Lower calcium concentrations in bone from high turnover (average degree of bone mineralization -6.2%, p<0.001) versus low turnover patients were observed. OLS-characteristics were distinctly different (p<0.01 to p<0.05) in patients with highest compared to those with lowest turnover. Patients with cinacalcet had different OLS-characteristics (p<0.05) compared to those without cinacalcet. Furthermore, patients with phosphate binders had differences in BMDD and OLS-characteristics (p<0.05) compared to patients without phosphate binders. CONCLUSIONS: Our findings suggest that in patients with CKD-MBD secondary hyperparathyroidism and increased bone turnover decrease the average degree of bone matrix mineralization. Conversely, density and lacunar size of the osteocytes are increased compared to adynamic bone disease pointing at distinct patterns of bone mineralization and osteocyte lacunar properties in these two disease entities.

A case report of severe calciphylaxis - suggested approach for diagnosis and treatment.

BACKGROUND: Calciphylaxis is a serious complication in patients with chronic kidney disease associated mineral and bone disorder. It can occur in conditions with low and high bone turnover. So far, there are no definite diagnostic and therapeutic guidelines which may prevent the devastating outcome in many calciphylaxis patients. We report a case which clearly illustrates that knowledge of the underlying bone disorder is essential for a directed treatment. Based on this experience we discuss a systematic diagnostic and therapeutic approach in patients with calciphylaxis. CASE PRESENTATION: We report a patient with severe calciphylaxis. Initial evaluation showed an elevated serum parathormone concentration and a bone-specific alkaline phosphatase activity in the upper normal range; however, the bone biopsy clearly showed adynamic bone disease. Extended dialysis with low calcium dialysate concentration and citrate anticoagulation, and administration of teriparatide led to a further increase in bone-specific alkaline phosphatase activity and most importantly, resulted in an activated bone turnover as confirmed by a second bone biopsy 11 weeks later. CONCLUSIONS: This case illustrates that laboratory tests cannot reliably differentiate between high and low bone turnover in calciphylaxis patients. More importantly, this case highlights the fact that specific therapies that alter bone metabolism cannot be applied without knowledge of the bone status. On this background, we suggest that bone biopsies should be an integral part in the diagnosis and therapeutic decision in these patients and should be evaluated in further studies.

Influence of angulation on metacarpal bone mineral density measurements using digital X-ray radiogrammetry.

OBJECTIVE: Digital X-ray radiogrammetry (DXR) is a computer-assisted technique used to quantify cortical bone density of the metacarpals. The influence of metacarpal bone rotation and type of cast material on bone mineral density (BMD) measurements using the DXR technique was tested. METHODS: The bone mineral density of the hand was measured by DXR, and rotation error (DXR-RE) as coefficients of variation were calculated, to verify reliability and reproducibility of this radiogeometric technique to assess in particular minor disease-related changes in the metacarpal bone mass. The reproducibility of the DXR measurements was also investigated using different cast materials (mull, elastic, and plastic). RESULTS: There were no significant changes in absolute values of DXR-BMD observed between 0 to [Formula: see text] angulation. The relative DXR-RE ranged between 0 % (degree 1) and 0.70 % (degrees 15 and 19) for DXR-BMD. Regarding the different cast materials, DXR-BMD revealed a coefficient of variation with 0.41 % (mull cast) and 0.21 % (elastic cast). For the plastic cast, the DXR technique was not able to perform an analysis of DXR-BMD. CONCLUSION: The study revealed no significant influence of metacarpal rotation on the measurements of metacarpal bone mineral density as estimated by DXR. DXR measurements are not optimal when cast material is used. DXR can accurately quantify periarticular cortical bone mass. This is significant especially for rheumatoid arthritis and related conditions where X-ray imaging of arthritic hands with varying degrees of deformity is performed.

Joint damage in rheumatoid arthritis: assessment of a new scoring method.

INTRODUCTION: The aim of this study was to assess a novel approach for the quantification of finger joint space narrowing and joint destruction in patients with rheumatoid arthritis (RA) focusing on the peripheral hand articulations. METHODS: A total of 280 patients with verified RA underwent computerized semi-automated measurements of joint space distance at the finger articulations based on radiographs. The Z-Score, which can differentiate between joint space alterations caused by RA versus age/gender-related changes, was calculated as a comparative parameter. The severity of joint space narrowing was also quantified by the Sharp Score. Sensitivity and specificity of the Z-Score (based on joint space widths differentiated for each peripheral finger joint) were evaluated to reveal the potential for the occurrence of erosions. Additionally, the potential of the Z-Score regarding the differentiation of therapeutic effects on joint space widths in patients under a therapy of methotrexate versus leflunomide was performed. RESULTS: The Z-Scores of finger articulations in patients with RA were generally decreased. Metacarpal-phalangeal (MCP) joint articulations showed a continuous significant decline of -1.65±0.30 standard deviations dependent on the Sharp Score. The proximal-interphalangeal joints also revealed a significant reduction of the Z-Score (-0.96±0.31 standard deviations). The sensitivity and specificity of MCP joint space distance for the detection of erosions were 85.4% versus 55.2%. The Sharp Score for joint space narrowing was not able to detect different treatments, whereas an accentuated stabilization of joint space narrowing could be identified for the Z-Score of the MCP joints in patients treated with leflunomide and methotrexate. CONCLUSION: The Z-Scoring method based on computer-aided analysis of joint space widths was able to reliably quantify severity-dependent joint space narrowing in RA patients. In the future, calculation of a Z-Score based on gender-specific and age-specific reference data shows the potential for a surrogate marker of RA progression that comprehends the early identification of patients with RA, and in particular those with erosive course of the disease, enabling a timely therapeutic strategy for cartilage protection.

The role of first-pass perfusion deficit in the detection of cardiac subendocardial manifestation in patients with autoimmune vasculitis.

This report describes the potential of cardiac magnetic resonance imaging (cMRI) based on myocardial first-pass perfusion imaging in the visualization of cardiac manifestations in autoimmune vasculitis, which in the heart are typically localized at the level of small subendocardial vessels. Two patients with primary or secondary autoimmune vasculitis were investigated in this study. Myocardial first-pass perfusion imaging was performed using an ECG-gated T1-weighted MRI sequence after the injection of intravenous bolus of gadolinium chelate. In both cases, the cMRI showed findings of subendocardial first-pass perfusion deficit (FPPD), a phenomenon so far described as microvascular obstruction (MVO) only in patients with acute cardiac infarction due to thromboembolic obstruction of small myocardial vessels. The two patients showed local subendocardial and myocardial hypoenhancement (characterized by a darker appearance than normal myocardial tissue), which is the typical morphological stigma of FPPD initially after injection of contrast media. The perfusion deficit, although morphologically very similar to the well-known phenomenon of MVO in acute cardiac infarction, was conceivably caused by different vasculitis-specific mechanisms such as occlusion of the microvasculature with erythrocytes, neutrophils and cellular debris. This study indicates that FPPD is useful for the non-invasive assessment of the microvasculature in patients with acute cardiac involvement in primary and secondary vasculitis.

The usefulness of computer-aided joint space analysis in the assessment of rheumatoid arthritis.

OBJECTIVE: Computer-aided joint space analysis (CAJSA) is a newly developed technique for the measurement of radiogeometrically detectable joint space widths of the metacarpal-phalangeal (JSD-MCP) and proximal-interphalangeal articulations (JSD-PIP). The aim of this study was to verify the sensitivity and specificity of these CAJSA measurements in the assessment of established RA. METHODS: Four hundred and fifty-eight participants (248 healthy subjects, 210 RA patients) underwent computerized semi-automated measurements of the JSD-MCP and JSD-PIP articulations (CAJSA, Radiogrammetry Kit, Version 1.3.6) based on digitally performed radiographs. The Sharp joint space narrowing score was also performed to determine RA-related joint space narrowing. RESULTS: The significant severity-dependent reduction for JSD-MCP was -44.0% and for JSD-PIP, -25.94% between Sharp scores 0 and 3. The sensitivity and specificity of JSD-MCP (total) was 88.1% versus 77.8%, respectively (AUC = 0.920; P < 0.001). Furthermore, JSD-PIP (total) revealed a lower sensitivity and specificity with 61.4% and 88.7% (AUC = 0.878; P < 0.001). CONCLUSION: The CAJSA method presented a reliable assessment of disease-related joint space narrowing in patients suffering from RA with excellent sensitivity and specificity. By providing quantitative data, other scoring methods could be significantly improved, and thereby the accuracy of the diagnosis and a better therapeutic evaluation could be achieved.

The balance between soluble receptors regulating IL-6 trans-signaling is predictive for the RANKL/osteoprotegerin ratio in postmenopausal women with rheumatoid arthritis.

The objective of this study is to investigate the relationship between soluble components of the interleukin 6 (IL-6) system mediating and modifying IL-6 trans-signaling and the RANKL-RANK-osteoprotegerin system in postmenopausal women with rheumatoid arthritis (RA). The following parameters were investigated in 126 postmenopausal women with RA: IL-6, soluble IL-6-receptor (sIL-6R), soluble glycoprotein 130 (sgp130), sRANKL, osteoprotegerin (OPG), osteocalcin, erythrocyte sedimentation rate and C-reactive protein in sera, pyridinolin and desoxypyridinolin crosslinks in the morning urine. Bone mineral density (BMD) was measured by dual X-ray absorptiometry at the lumbar spine (BMD-LS) and at the femoral neck (BMD-FN). Predictors of RANKL/OPG ratio and BMD were evaluated by multiple linear regression analysis. The following determinants of the RANKL/OPG ratio were identified: sIL-6R/sgp130 ratio and daily glucocorticoid (GC) dose as positive determinants in the whole group (R (2) = 0.56; P = 0.001), sIL-6R/sgp130 ratio as the exclusive positive determinant in patients with GC therapy (R (2) = 0.48; P = 0.001) and sgp130 as negative determinant in patients without GC (R (2) = 0.42; P = 0.031). Sgp130 was highly significantly positively correlated with OPG in the whole group (P < 0.001) as well as in patients with (n = 70; P < 0.05) and without GC therapy (n = 56; P < 0.01). sIL-6R was the main negative predictor of BMD-LS (R (2) = 0.41; P = 0.019). High sIL-6R/sgp130 ratio and/or low sgp130 are associated with a high sRANKL/OPG ratio in sera of postmenopausal women with RA indicating the critical significance of IL-6 trans-signaling for an increase in the RANKL/OPG ratio and of bone resorption. Inhibition of IL-6 trans-signaling may be an effective bone-protecting principle in postmenopausal women with RA.

Reproducibility and influence of hand rotation on computer-aided joint space analysis.

OBJECTIVES: Computer-aided joint space analysis (CAJSA) is a recently developed, semi-automated tool to aid in the measurement of joint space margins based on hand radiographs. The objective of this study is to verify the potential effect of hand rotation during X-ray imaging on the measurement of joint space width using CAJSA and to evaluate the reproducibility of the CAJSA technique in healthy subjects and in patients with rheumatoid arthritis. METHODS: All joint space distance (JSD) measurements were performed using CAJSA-technology at the metacarpophalangeal articulation based on conventional and digital hand radiographs. RESULTS: I. Hand rotation showed an effect on the reproducibility with CV ranging between 0.39% (angulation 1°) and 1.66% (angulation 19°). II. Regarding the overall reproducibility of the CAJSA method, the intra-radiograph reproducibility of JSD was calculated with CV=0.54% for conventional images and CV=0.38% for digital images. The inter-radiograph reproducibility error was observed with CV=0.66% (conventional images) and CV=0.63% (digital images). III. The study revealed a reproducibility for CAJSA measurements in RA ranging between 0.37% (JSD-MCP ring finger; van der Heijde-modification of the Sharp method score 1) to 1.37% (JSD-MCP index finger; van der Heijde-modification of the Sharp method score 3). CONCLUSION: CAJSA measures JSD at the metacarpophalangeal articulation with high reproducibility in healthy subjects and in patients with differing stages of rheumatoid arthritis. Additional findings show that hand rotation during X-ray imaging has an impact on the CAJSA measurements; thus avoiding acquisition of hand radiographs with a rotation error of more than 15 degrees can be recommended.

Treatment of bone loss in patients with chronic liver disease awaiting liver transplantation.

BACKGROUND: Most of the patients awaiting liver transplantation already have osteopenia or even osteoporosis by end-stage liver disease.In a retrospective study, we investigated the effect of pre-treatment with oral monthly ibandronate (150 mg), vitamin D3 (800 IU/day) and calcium (1 g/day) for osteopenia and osteoporosis caused by end-stage liver disease in patients before and after liver transplantation (LT). METHODS: The bone mineral density (BMD) of the lumbar spine (LS) and the femoral neck was measured prospectively pre- and post-LT in 31 patients with existing pre-transplant osteopenia. Patients had osteopenia of the LS prior to LT (T-score -1.8 ± 1.5) so that the treatment medication was initiated immediately after the diagnosis. RESULTS: The study group showed a permanently increased BMD with significant differences (g/cm²) from baseline up to 12 months post LT at the lumbar spine (LS: pre-LT 0.80 ± 0.11 g/cm², three months: 0.90 ± 0.08 (P <0.005); six months: 0.95 ± 0.11 (P < 0.008); 12 months: 1.00 ± 0.09 -0.85 (P <0.012). CONCLUSION: The combined pre- and post-operative treatment with oral ibandronate had significantly improved bone mineral density of the lumbar spine at 3, 6 and 12 months post LT. The immediate post-operative bone loss after LT can be significantly avoided by pre-treatment of liver transplant candidates affected by osteopenia.

Feasibility study of semi-automated measurements of finger joint space widths.

The purpose of this study is to evaluate technical feasibility based on image capturing conditions (film-focus distance (FFD), film sensitivity, film brand, exposure level and tube voltage) that potentially alter radiographs and consequently may influence the semi-automated measurement of joint space distance (JSD) by computer-aided joint space analysis (CAJSA) in rheumatoid arthritis and osteoarthritis. The radiographs of a left hand (deceased man) were acquired under systematically changing image capturing conditions (exposure level: 4-8 mAs; FFD: 90-130 cm; film sensitivity: 200/400 and tube voltage: 40-52 kV with different image modalities: conventional radiographs, original digital radiographs, digital print-outs). All JSD-measurements were performed with the CAJSA-technology (Radiogrammetry Kit, Version 1.3.6; Sectra; Sweden) at the metacarpal-phalangeal articulation. JSD-analysis was not influenced by changes of FFD, exposure level, film sensitivity or film brand. JSD showed significant variation caused by tube voltage (conventional: CV = 1.913% for Agfa and CV = 2.448% for Kodak; digital: CV = 0.741% for Philips print-outs and CV = 0.620% with original digital images versus CV = 2.185% for Siemens print-outs and 0.951% with original digital images). Computer-aided joint space analysis for JSD-measurements is unaffected by the following image capturing parameters: film-focus distance, film sensitivity, film brand and exposure level. An influence of tube voltage was detected in a lesser extent for original digital images compared to the printed digital as well as conventional versions. Consequently, a standardized tube voltage is essential for accurate reproductions of CAJSA-measurements in rheumatoid arthritis and osteoarthritis.

Treatment of osteoporosis after liver transplantation with ibandronate.

Osteoporosis is a major side-effect after liver transplantation (LTX). Therefore, the objective of the study was to evaluate the efficacy of ibandronate to reduce fractures after LTX. Seventy-four patients after LTX were included in the study and measurements of bone mineral density (BMD) of lumbar spine and proximal femur using dual energy X-ray absorptiometry (DEXA) were performed prior to and 3, 6, 12 and 24 months after surgery. The study group (IBA) consisted of 34 patients who received calcium (1 g/day), vitamin D3 (800-1000 IE/day) and ibandronate 2 mg every 3 months intravenously for 1 year. The control group consisted of 40 patients (CON) who received calcium and vitamin D3 at the same dosages. Prevalence of new fractures was predefined as primary endpoint. Changes of BMD and biochemical markers of bone metabolism were also investigated. In all patients, we found a reduction of BMD in the first few months after LTX. In the lumbar spine and the proximal femur the maximum reduction occurred 3 and 6 months post-LTX. One and 2 years after transplantation, the group receiving ibandronate demonstrated a better recovery from loss of BMD and a significantly lower prevalence of fractures (IBA 2 vs. CON 10 P < 0.04, chi(2)). Ibandronate with calcium and vitamin D3 reduces the BMD-loss after LTX and decreases the rate of bone fractures significantly.

Implementation of Z-scores as an age- and sex-independent parameter for estimating joint space widths in rheumatoid arthritis.

OBJECTIVE: To compare normative data of joint space distances (JSD) with the JSD of patients with rheumatoid arthritis (RA) as measured by computer-aided joint space analysis (CAJSA) at the metacarpophalangeal (MCP) articulations, and to differentiate age- and sex-related alterations from the disease-related joint space narrowing. METHODS: In total, 256 healthy subjects and 248 patients with verified RA (following revised ACR criteria) underwent computerized semiautomated measurements of JSD (CAJSA, version 1.3.6) at the MCP articulation (JSD-MCP) based on digital radiographs. The Z-score, a comparative parameter that differentiates joint space alterations caused by RA-related cartilage destruction from age- and sex-related changes, was calculated. RESULTS: Our data showed a relationship between measured joint space widths (MCP total and MCP thumb to little finger) and age for healthy subjects and also the RA group. The RA group revealed an age-related joint space narrowing that was surpassed by the RA-related narrowing of joint space widths classified by Sharp joint space narrowing score and resulting in smaller Z-scores for RA patients. CONCLUSION: The CAJSA technique seems to distinguish age-related JSD changes in healthy volunteers from RA-induced alterations. In addition the Z-score was also able to differentiate RA-dependent narrowing of JSD. Calculation of the Z-scores based on sex- and age-specific reference data may facilitate earlier identification of patients with RA, allowing initiation of a more optimal, individually adapted therapeutic strategy.

Temperature influence on DXA measurements: bone mineral density acquisition in frozen and thawed human femora.

BACKGROUND: Determining bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) is an established and widely used method that is also applied prior to biomechanical testing. However, DXA is affected by a number of factors. In order to delay decompositional processes, human specimens for biomechanical studies are usually stored at about -20 degrees C; similarly, bone mineral density measurements are usually performed in the frozen state. The aim of our study was to investigate the influence of bone temperature on the measured bone mineral density. METHODS: Using DXA, bone mineral density measurements were taken in 19 fresh-frozen human femora, in the frozen and the thawed state. Water was used to mimic the missing soft tissue around the specimens. Measurements were taken with the specimens in standardized internal rotation. Total-BMD and single-BMD values of different regions of interest were used for evaluation. RESULTS: Fourteen of the 19 specimens showed a decrease in BMD after thawing. The measured total-BMD of the frozen specimens was significantly (1.4%) higher than the measured BMD of the thawed specimens. CONCLUSION: Based on our findings we recommend that the measurement of bone density, for example prior to biomechanical testing, should be standardized to thawed or frozen specimens. Temperature should not be changed during measurements. When using score systems for data interpretation (e.g. T- or Z-score), BMD measurements should be performed only on thawed specimens.