MRI underestimates presence and size of knee osteophytes using CT as a reference standard.

OBJECTIVE: To explore the diagnostic performance of routine magnetic resonance imaging (MRI) for the cross-sectional assessment of osteophytes (OPs) in all three knee compartments using computed tomography (CT) as a reference standard. METHODS: The Strontium Ranelate Efficacy in Knee Osteoarthritis (SEKOIA) trial explored the effect of 3 years of treatment with strontium ranelate in patients with primary knee OA. OPs were scored for the baseline visit only using a modified MRI Osteoarthritis Knee Score (MOAKS) scoring system in the patellofemoral (PFJ), the medial tibiofemoral (TFJ) and the lateral TFJ. Size was assessed from 0 to 3 in 18 locations. Descriptive statistics were used to describe differences in ordinal grading between CT and MRI. In addition, weighted-kappa statistics were employed to assess agreement between scoring using the two methods. Sensitivity, specificity, positive predictive value and negative predictive value as well as area under the curve (AUC) measures of diagnostic performance were employed using CT as the reference standard. RESULTS: Included were 74 patients with available MRI and CT data. Mean age was 62.9 ± 7.5 years. Altogether 1,332 locations were evaluated. For the PFJ, MRI detected 141 (72%) of 197 CT-defined OPs with a w-kappa of 0.58 (95% CI [0.52-0.65]). In the medial TFJ, MRI detected 178 (81%) of 219 CT-OPs with a w-kappa of 0.58 (95% CI [0.51-0.64]). For the lateral compartment these numbers were 84 (70%) of 120 CT-OPs with a w-kappa of 0.58 (95% CI [0.50-0.66]). CONCLUSION: MRI underestimates presence of osteophytes in all three knee compartments. CT may be helpful particularly regarding assessment of small osteophytes particularly in early disease.

The clinical application of high-resolution peripheral computed tomography (HR-pQCT) in adults: state of the art and future directions.

High-resolution peripheral computed tomography (HR-pQCT) was developed to image bone microarchitecture in vivo at peripheral skeletal sites. Since the introduction of HR-pQCT in 2005, clinical research to gain insight into pathophysiology of skeletal fragility and to improve prediction of fractures has grown. Meanwhile, the second-generation HR-pQCT device has been introduced, allowing novel applications such as hand joint imaging, assessment of subchondral bone and cartilage thickness in the knee, and distal radius fracture healing. This article provides an overview of the current clinical applications and guidance on interpretation of results, as well as future directions. Specifically, we provide an overview of (1) the differences and reference data for HR-pQCT variables by age, sex, and race/ethnicity; (2) fracture risk prediction using HR-pQCT; (3) the ability to monitor response of anti-osteoporosis therapy with HR-pQCT; (4) the use of HR-pQCT in patients with metabolic bone disorders and diseases leading to secondary osteoporosis; and (5) novel applications of HR-pQCT imaging. Finally, we summarize the status of the application of HR-pQCT in clinical practice and discuss future directions. From the clinical perspective, there are both challenges and opportunities for more widespread use of HR-pQCT. Assessment of bone microarchitecture by HR-pQCT improves fracture prediction in mostly normal or osteopenic elderly subjects beyond DXA of the hip, but the added value is marginal. The prospects of HR-pQCT in clinical practice need further study with respect to medication effects, metabolic bone disorders, rare bone diseases, and other applications such as hand joint imaging and fracture healing. The mostly unexplored potential may be the differentiation of patients with only moderately low BMD but severe microstructural deterioration, which would have important implications for the decision on therapeutical interventions.

Heterogenous bone response to biologic DMARD therapies in rheumatoid arthritis patients and their relationship to functional indices.

Objectives: Previous studies of high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging of hand joints in patients with rheumatoid arthritis (RA) have suggested that erosion healing may occur. Our objective was to examine changes in erosion volume, joint space width (JSW), bone mineral density (BMD), and bone remodelling, and their association with clinical outcomes and measures of patient hand function.Method: We examined 48 patients who achieved a good response to a newly initiated biologic therapy. HR-pQCT images of the dominant hands' second and third metacarpophalangeal joints were obtained 3 and 12 months after therapy initiation. Bone erosion volume, JSW, BMD, and bone remodelling were quantified from HR-pQCT images, with improvement, no change (unchanged), or progression in these measures determined by least significant change. Disease activity and hand function measures were collected.Results: There were no significant group changes in HR-pQCT outcomes over the 9 month period. Twenty-two patients had total erosion volumes that remained unchanged, nine showed improvement, and two progressed. The majority of JSW and BMD measures remained unchanged. There was a significant association between the baseline Health Assessment Questionnaire score and the change in minimum JSW, but no other significant associations between HR-pQCT outcomes and function were observed.Conclusions: The vast majority of patients maintained unchanged JSW and BMD over the course of follow-up. Significant improvements in total erosion volume occurred in 27% of patients, suggesting that biologic therapies may lead to erosion healing in some patients, although this did not have an impact on self-reported and demonstrated hand function.

Guidelines for the assessment of bone density and microarchitecture in vivo using high-resolution peripheral quantitative computed tomography.

INTRODUCTION: The application of high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess bone microarchitecture has grown rapidly since its introduction in 2005. As the use of HR-pQCT for clinical research continues to grow, there is an urgent need to form a consensus on imaging and analysis methodologies so that studies can be appropriately compared. In addition, with the recent introduction of the second-generation HrpQCT, which differs from the first-generation HR-pQCT in scan region, resolution, and morphological measurement techniques, there is a need for guidelines on appropriate reporting of results and considerations as the field adopts newer systems. METHODS: A joint working group between the International Osteoporosis Foundation, American Society of Bone and Mineral Research, and European Calcified Tissue Society convened in person and by teleconference over several years to produce the guidelines and recommendations presented in this document. RESULTS: An overview and discussion is provided for (1) standardized protocol for imaging distal radius and tibia sites using HR-pQCT, with the importance of quality control and operator training discussed; (2) standardized terminology and recommendations on reporting results; (3) factors influencing accuracy and precision error, with considerations for longitudinal and multi-center study designs; and finally (4) comparison between scanner generations and other high-resolution CT systems. CONCLUSION: This article addresses the need for standardization of HR-pQCT imaging techniques and terminology, provides guidance on interpretation and reporting of results, and discusses unresolved issues in the field.

Treatment of bone loss in proximal femurs of postmenopausal osteoporotic women with AGN1 local osteo-enhancement procedure (LOEP) increases hip bone mineral density and hip strength: a long-term prospective cohort study.

This first-in-human study of AGN1 LOEP demonstrated that this minimally-invasive treatment durably increased aBMD in femurs of osteoporotic postmenopausal women. AGN1 resorption was coupled with new bone formation by 12 weeks and that new bone was maintained for at least 5-7 years resulting in substantially increased FEA-estimated femoral strength. INTRODUCTION: This first-in-human study evaluated feasibility, safety, and in vivo response to treating proximal femurs of postmenopausal osteoporotic women with a minimally-invasive local osteo-enhancement procedure (LOEP) to inject a resorbable triphasic osteoconductive implant material (AGN1). METHODS: This prospective cohort study enrolled 12 postmenopausal osteoporotic (femoral neck T-score ≤ - 2.5) women aged 56 to 89 years. AGN1 LOEP was performed on left femurs; right femurs were untreated controls. Subjects were followed-up for 5-7 years. Outcomes included adverse events, proximal femur areal bone mineral density (aBMD), AGN1 resorption, and replacement with bone by X-ray and CT, and finite element analysis (FEA) estimated hip strength. RESULTS: Baseline treated and control femoral neck aBMD was equivalent. Treated femoral neck aBMD increased by 68 ± 22%, 59 ± 24%, and 58 ± 27% over control at 12 and 24 weeks and 5-7 years, respectively (p < 0.001, all time points). Using conservative assumptions, FEA-estimated femoral strength increased by 41%, 37%, and 22% at 12 and 24 weeks and 5-7 years, respectively (p < 0.01, all time points). Qualitative analysis of X-ray and CT scans demonstrated that AGN1 resorption and replacement with bone was nearly complete by 24 weeks. By 5-7 years, AGN1 appeared to be fully resorbed and replaced with bone integrated with surrounding trabecular and cortical bone. No procedure- or device-related serious adverse events (SAEs) occurred. CONCLUSIONS: Treating femurs of postmenopausal osteoporotic women with AGN1 LOEP results in a rapid, durable increase in aBMD and femoral strength. These results support the use and further clinical study of this approach in osteoporotic patients at high risk of hip fracture.

Cartilage morphology assessed by high resolution micro-computed tomography in non OA knees.

OBJECTIVE: At the microscopic level, there is no established 3D method to measure cartilage volume and thickness. An easy, precise and accurate volume and thickness measurements of human cartilage has been developed from micro-computed tomography (micro-CT) images. DESIGN: In the medial tibial plateau of twenty nine left cadaveric knees classified as normal, vertical cores (7 mm in diameter) were extracted in three locations: lateral (LAT), medial posterior (MP) and medial anterior (MA). The cores were imaged in mineral oil with micro-CT (voxel size 10.2 µm) and were measured cartilage volume (Cart.Vol, mm(3)) and cartilage thickness (Cart.Th, mm) using a thickness plugin. Short term reproducibility and standard deviation (ST_RMSCV%, ST_RMSSD, mm) were determined. To assess accuracy, holes with diameters of 2 mm, 3 mm, and 4 mm were artificially generated and nominal and measured hole sizes were compared. RESULTS: Precision of Cart.Vol_ST_RMSCV% was 1.35%. The mean biases between nominal hole volume and measurements were -0.49 ± 1.5 mm(3) (2 mm), -0.41 ± 4.2 mm(3) (3 mm) and +0.34 ± 4.4 mm(3) (4 mm). ST_RMSSD was 100 times lower than the biological variation and the highest bias to measure volume was 24 times lower. Cart.Th results statistically differed among core extraction locations: 1.75 ± 0.28 mm (LAT), 1.84 ± 0.40 mm (MP) and 2.32 ± 0.41 mm (MA). CONCLUSION: With a standard laboratory micro-CT system, it was possible to measure cartilage volume and thickness with good precision and accuracy relative to the biological variation of the specimen cohort. Cartilage measurements from micro-CT probably will improve the knowledge of the relationship between cartilage and subchondral bone and may allow to better understand the OA process.

Prevalence of sarcopenic obesity in Germany using established definitions: Baseline data of the FORMOsA study.

UNLABELLED: The prevalence of sarcopenic obesity in community-dwelling women 70 years and older according to established sarcopenia and obesity definitions averaged between 0 and 2.3 % and can thus be considered as relatively low. However, the converse argument that sarcopenic obesity was incompatible with an independent life cannot be confirmed. INTRODUCTION: The primary aim of the study was to determine the prevalence of sarcopenic obesity (SO) in community-dwelling (CD) older females in Germany. The secondary aim was to assess whether these females really live independently and autonomously. METHODS: A total of 1325 CD females 70 years and older living in the area of Erlangen-Nürnberg, Germany were assessed. Sarcopenia as defined by (a) the European Working Group on Sarcopenia in older people (EWGSOP) and (b) the International working group on Sarcopenia (IWGS) combined with obesity defined as (a) BMI ≥ 30 kg/m(2) (NIH) or (b) body-fat ≥ 35 % (WHO) was determined. In participants with SO, Barthel Index, care level and social network were retrospectively evaluated via personal interview. RESULTS: Based on anthropometric data, family, education and social status, lifestyle, number and distribution of diseases and medication, the present cohort is representative for the corresponding German population. Sarcopenia prevalence was 4.5 % according to EWGSOP and 3.3 % according to the IWGS criteria. Obesity prevalence in our cohort averaged 19.8 % (BMI, NIH) and 63.8 % (body fat, WHO). The overlap between both factors (i.e. SO) ranged from 0 % (EWGSOP + NIH criteria) to 2.3 % (EWGSOP + WHO criteria). Factors that may represent limited autonomy or independence were very rarely identified in this SO cohort. CONCLUSION: The prevalence of sarcopenic obesity in the CD (female) German population 70 years + is relatively low. With respect to our second research aim, the hypothesis that SO was incompatible with independent life was rejected. However, the latter finding should be addressed with more dedicated study designs.

QCT of the proximal femur--which parameters should be measured to discriminate hip fracture?

SUMMARY: For quantitative computed tomography (QCT), most relevant variables to discriminate hip fractures were determined. A multivariate analysis showed that trabecular bone mineral density (BMD) of the trochanter with "cortical" thickness of the neck provided better fracture discrimination than total hip integral BMD. A slice-by-slice analysis of the neck or the inclusion of strength-based parameters did not improve fracture discrimination. INTRODUCTION: For QCT of the proximal femur, a large variety of analysis parameters describing bone mineral density, geometry, or strength has been considered. However, in each given study, generally just a small subset was used. The aim of this study was to start with a comprehensive set and then select a best subset of QCT parameters for discrimination of subjects with and without acute osteoporotic hip fractures. METHODS: The analysis was performed using the population of the European Femur Fracture (EFFECT) study (Bousson et al. J Bone Min Res: Off J Am Soc Bone Min Res 26:881-893, 2011). Fifty-six female control subjects (age 73.2 ± 9.3 years) were compared with 46 female patients (age 80.9 ± 11.1 years) with acute hip fractures. The QCT analysis software MIAF-Femur was used to virtually dissect the proximal femur and analyze more than 1000 parameters, predominantly in the femoral neck. A multivariate best-subset analysis was used to extract the parameters best discriminating hip fractures. All results were adjusted for age, height, and weight differences between the two groups. RESULTS: For the discrimination of all proximal hip fractures as well as for cervical fractures alone, the measurement of neck parameters suffices (area under the curve (AUC) = 0.84). Parameters characterizing bone strength are discriminators of hip fractures; however, in multivariate models, only "cortical" cross-sectional area in the neck center remained as a significant contributor. The combination of one BMD parameter, trabecular BMD of the trochanter, and one geometry parameter, "cortical" thickness of the neck discriminated hip fracture with an AUC value of 0.83 which was significantly better than 0.77 for total femur BMD alone. A comprehensive slice-based analysis of the neck along its axis did not significantly improve hip fracture discrimination. CONCLUSIONS: If QCT of the hip is performed, the analysis should include neck and trochanter. In particular, for fractures of any type, a comprehensive slice-based analysis of the neck along its axis did not significantly improve hip fracture discrimination nor did the inclusion of strength-related parameters other than "cortical" area or thickness. One BMD and one geometry parameter, in this study, the combination of trabecular BMD of the trochanter and of "cortical" thickness of the neck resulted in significant hip fracture discrimination.

Whole-body electromyostimulation to fight sarcopenic obesity in community-dwelling older women at risk. Resultsof the randomized controlled FORMOsA-sarcopenic obesity study.

The effect of whole body-electromyostimulation in community-dwelling women ≥70 with sarcopenic obesity was heterogeneous, with high effects on muscle mass, moderate effects on functional parameters, and minor effects on fat mass. Further, we failed to determine a supportive effect of additional protein-enriched dietary supplementation in this albeit predominately well-nourished group. INTRODUCTION: The aim of the study was to determine the effect of whole-body electromyostimulation (WB-EMS) on sarcopenic obesity (SO) in community-dwelling women more than 70 years with sarcopenic obesity. METHODS: Seventy-five community-dwelling women ≥70 years with SO were randomly allocated to either a WB-EMS-application with (WB-EMS &P; 24.9 ± 1.9 kg/m2) or without (WB-EMS; 25.2 ± 1.8 kg/m2) dietary supplementation (150 kcal/day, 56 % protein) or a non-training control group (CG; 24.7 ± 1.4 kg/m2). WB-EMS consisted of one weekly session of 20 min (85 Hz, 350 µs, 4 s of strain-4 s of rest) performed with moderate to high intensity. Primary study endpoint was the Sarcopenia Z-Score constituted by skeletal muscle mass index (SMI, as assessed by dual energy X-ray absorptiometry), grip strength, and gait speed, and secondary study endpoint was body fat (%). RESULTS: Sarcopenia Z-score comparably increases in the WB-EMS and the WB-EMS&P-group (p ≤ .046). Both groups differ significantly (p ≤ .001) from the CG which deteriorated significantly (p = .006). Although body fat changes were most pronounced in the WB-EMS (-0.9 ± 2.1; p = .125) and WB-EMS&P (-1.4 ± 2.5; p = .028), reductions did not statistically differ (p = .746) from the CG (-0.8 ± 2.7; p = .179). Looking behind the covariates, the most prominent changes were determined for SMI, with a significant increase in both EMS-groups (2.0-2.5 %; p ≤ .003) and a decrease in the CG (-1.2 ± 3.1 %; p = .050) with significant between-group differences (p = .001). CONCLUSION: WB-EMS is a safe and attractive method for increasing muscle mass and functional capacity in this cohort of women 70+ with SO; however, the effect on body fat is minor. Protein-enriched supplements did not increase effects of WB-EMS alone.

A low-radiation exposure protocol for 3D QCT of the spine.

SUMMARY: Cadaver and phantom measurements and simulations confirmed that radiation exposure in 3D QCT of the spine can be reduced if 80 kV instead of 120 kV protocols are used; 120 mAs and slice thicknesses of 1-1.3 mm should be usable but obese patient will require higher milliampere-second settings. PURPOSE: To develop a low-radiation exposure CT acquisition protocol for 3D QCT of the thoracolumbar spine. METHODS: Twenty-six cadavers were scanned with a standard protocol of 120 kV, 100 mAs and with a low-dose protocol using 90 kV, 150 mAs. The scan range included the vertebrae T6 to L4. Each vertebra was segmented and the integral volume and BMD of the total vertebral body were determined. Effective dose values were estimated. The impact of milliampere-second reduction on image quality was simulated by adding noise. RESULTS: One hundred ninety-six vertebrae were analyzed. Integral volume as well as integral BMD correlated significantly (p < 0.001) between standard and low-dose protocols (volume, r (2) = 0.991, residual root mean square (RMS) error, 0.77 cm(3); BMD, r (2) = 0.985, RMS error, 4.21 mg/cm(3)). The slope significantly differed from 1 for integral BMD but not for volume hinting at residual field inhomogeneity differences between the two voltage settings that could be corrected by cross-calibration. Compared to the standard protocol, effective dose was reduced by over 50 % in the low-dose protocol. Adding noise in the 90 kV images to simulate a reduction from 150 to 100 mAs did not affect the results for integral volume or BMD. CONCLUSIONS: For 3D QCT of the spine, depending on scanner type, 80 or 90 kV instead of 120 kV protocols may be considered as an important option to reduce radiation exposure; 120 mAs and slice thicknesses of 1-1.5 mm are usable if segmentation is robust to noise. In obese patients, higher milliampere-second settings will be required.

Accuracy of trabecular structure by HR-pQCT compared to gold standard µCT in the radius and tibia of patients with osteoporosis and long-term bisphosphonate therapy.

UNLABELLED: Despite an increasing use of high-resolution peripheral quantitative computed tomography (HR-pQCT) to evaluate bone morphology in vivo, there are reservations about its applicability in patients with osteoporosis and antiresorptive therapy. This study shows that HR-pQCT provides acceptable in vivo accuracy for bone volume fraction (BV/TV) in patients with osteoporosis and bisphosphonate (BP) treatment. INTRODUCTION: The primary aim was to analyze agreement of trabecular structure between HR-pQCT and gold standard microtomography (µCT) in patients with osteoporosis and long-term BP therapy. METHODS: In the BioAsset study, we analyzed cadaver radii and tibiae of 34 postmenopausal females (81.1 ± 7.1 years) with osteoporosis (no BP n = 22, 1-5 years BP n = 5, >5 years BP n = 7). Two HR-pQCT protocols (patient-mode and µCT-mode) were compared with gold standard µCT after image registration. Undecalcified histological sections were obtained to quantify nonmineralized bone matrix. Bland-Altman plots illustrated methodological agreement. Multiple regression analysis was used to test for variables associated with method agreement. RESULTS: In the radius and tibia, patient-mode HR-pQCT derived indices including bone volume fraction, trabecular number, and trabecular separation correlated well with gold standard µCT (R(2) = 0.78 - 0.88) except for trabecular thickness (R(2) = 0.11). Bland-Altman plots illustrated adequate agreement for bone volume fraction. Lower agreement of trabecular number and trabecular separation improved with decreasing structural impairment at the tibia only. Trabecular thickness was not appropriately assessed with HR-pQCT at both skeletal sites. Higher agreement for bone volume fraction was associated with increasing tissue mineral density in the tibia. CONCLUSIONS: HR-pQCT provides acceptable in vivo accuracy for BV/TV in patients with osteoporosis and BP treatment. Higher TMD was associated with higher BV/TV accuracy in vivo. Overall, methodological agreement got less accurate with increasing structural impairment in the tibia.

Bone marrow lesions identified by MRI in knee osteoarthritis are associated with locally increased bone mineral density measured by QCT.

OBJECTIVE: Bone marrow lesions (BMLs) in the knee are associated with pain and compartment-specific joint space narrowing. However, the correlation of BMLs with bone mineral density (BMD) has rarely been investigated. The aim of the present study was to examine whether BMD in BMLs is altered compared to the surrounding bone. DESIGN: Thirty-four BMLs detected in osteoarthritis (OA) knees (KL grade 2 and 3) of 26 patients were investigated. A 3D-segmentation was used to determine BML volumes of interest (VOI) and their surrounding bone in MR images. These VOIs were registered to corresponding single-energy QCT images and a BMD analysis was performed. The same VOIs were transferred to control datasets (19 OA patients without BMLs) by an elastic registration, where the BMD analysis was repeated. To account for the dependence of bone marrow composition on BMD measures derived using single-energy QCT, simulations were performed to evaluate how changing fat-water compositions likely occurring with BML development may influence BMD measures and observed BMD differences between patients with and without BMLs. The association between loading in the knee and the occurrence of BMLs was investigated by medial to lateral (M:L) BMD ratios. RESULTS: BMD was significantly increased at BML locations, even with a fat-to-water conversion rate of 39%. The M:L BMD ratio was significantly increased in bones with medial BMLs. CONCLUSIONS: BMD was examined exactly at BML locations and surrounding bone using highly accurate segmentation and registration methods. BMD was significantly increased at BML locations (P < 0.05).

Second primary malignancies in head and neck cancer patients: high prevalence of curable-stage disease.

BACKGROUND AND PURPOSE: Patients treated for squamous cell carcinoma of the head and neck (HNSCC) carry a high risk of second primary malignancies (SPM). Recently, computed tomography (CT) of the chest was shown to significantly decrease the risk of death due to bronchial carcinoma (BC) in a cohort of smokers whose risk of BC is increased but might be lower than that of patients previously treated for HNSCC. Thus, the present study evaluated the potential benefit of CT and other examinations in the detection of SPM in HNSCC patients. PATIENTS AND METHODS: Between July 2008 and November 2011, 118 participants underwent a prospective, systematic examination for SPM (13 women, 105 men, median age 62 years). All patients had been previously treated for HNSCC and showed no recurrence or distant metastases at the time of the study start. CT scans, ear-nose-throat endoscopy, and endoscopy of the esophagus and stomach were performed. RESULTS: Overall, 33 suspicious findings were clarified by additional investigations. In all, 26 SPM were confirmed in 21 of 118 patients (18%; 10 lung, 7 HNSCC, 3 gastrointestinal, 1 renal). Eighteen of these 21 patients (86%) underwent therapy with curative intent. CONCLUSION: The examinations revealed a high prevalence of curable stage SPM in HNSCC patients. Adapting a surveillance scheme including a chest CT is recommended.

Advanced CT based in vivo methods for the assessment of bone density, structure, and strength.

Based on spiral 3D tomography a large variety of applications have been developed during the last decade to asses bone mineral density, bone macro and micro structure, and bone strength. Quantitative computed tomography (QCT) using clinical whole body scanners provides separate assessment of trabecular, cortical, and subcortical bone mineral density (BMD) and content (BMC) principally in the spine and hip, although the distal forearm can also be assessed. Further bone macrostructure, for example bone geometry or cortical thickness can be quantified. Special high resolution peripheral CT (hr-pQCT) devices have been introduced to measure bone microstructure for example the trabecular architecture or cortical porosity at the distal forearm or tibia. 3D CT is also the basis for finite element analysis (FEA) to determine bone strength. QCT, hr-pQCT, and FEM are increasingly used in research as well as in clinical trials to complement areal BMD measurements obtained by the standard densitometric technique of dual x-ray absorptiometry (DXA). This review explains technical developments and demonstrates how QCT based techniques advanced our understanding of bone biology.

Effect of block-periodized exercise training on bone and coronary heart disease risk factors in early post-menopausal women: a randomized controlled study.

The purpose of this 12 month randomized exercise intervention was to determine the effect of a block-periodized multipurpose exercise program on bone mineral density (BMD) and parameters of the metabolic syndrome (MetS) in early post-menopausal women. Eighty-five subjects (52.3 ± 2.4 years) living in the area of Erlangen (Germany) were randomly assigned into an exercise (EG, n=43) or a wellness-control group (CG: n=42). The EG performed a periodized multipurpose exercise program with 4-6-week blocks of high-intensity bone-specific exercise intermitted by 10-12 weeks of exercise dedicated to increase endurance and reduce cardiac and metabolic risk factors. The CG performed a low-volume/low-intensity "wellness" program to increase well-being. After 12 months, significant exercise effects were observed for the lumbar spine (LS) BMD as assessed by quantitative computed tomography [total BMD (EG: -0.3 ± 2.1% vs CG: -2.1 ± 2.2%, P=0.015); trabecular BMD (EG: -0.7 ± 3.4% vs CG: -4.7 ± 4.9%, P=0.001) and dual-energy x-ray absorptiometry (DXA) (EG: -0.1 ± 2.2% vs CG: -2.0 ± 2.0%, P=0.002)]. However, no significant effects were observed for total hip BMD as assessed by DXA (P=0.152). Although all MetS parameters were favorably affected among the EG, only the effect for waist circumference was significant. In summary, short periods of bone-specific intervention embedded in longer periods of exercises dedicated to improve cardiovascular and metabolic risk factors positively affected BMD at the LS.

[Interstitial lung diseases (ILD) in smokers: spectrum in high resolution computed tomography (HRCT)]. / Interstitielle Lungenerkrankungen (ILD) bei Rauchern : Spektrum in der hochauflösenden Computertomographie (HRCT).

Smoking is a known risk factor for the development of various interstitial lung diseases, e.g. respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and pulmonary Langerhans cell histiocytosis. These disorders frequently present with overlapping clinical pathological features and in addition may coexist within the same patient. In the clinical routine the differential diagnosis may be challenging or even impossible; therefore, smoking-related lung diseases are considered as part of the same disease spectrum representing different degrees of lung parenchymal damage secondary to cigarette smoke exposure. The role of cigarette smoking in the development of pulmonary fibrosis is complex and subject to intense investigation. It encompasses a subset of patients with nonspecific interstitial pneumonia where cigarette smoking may have played a causative role as well as patients with combined pulmonary fibrosis and emphysema (CPFE) as a novel entity with clearly defined clinical radiological features.

CT imaging for the investigation of subchondral bone in knee osteoarthritis.

In osteoarthritis, magnetic resonance imaging is the method of choice to image articular cartilage and "bone marrow lesions." However, the calcified cartilage, the subchondral bone plate, and trabecular subchondral bone that are mineralized tissues strongly attenuate X-rays and are therefore potentially accessible for analyses using computed tomography (CT). CT images nicely show osseous cardinal signs of advanced osteoarthritis such as osteophytes, subchondral cysts, and subchondral bone sclerosis. But more importantly, CT can help us to better understand the pathophysiology of knee osteoarthritis from the measurement of the density and structure of subchondral mineralized tissues in vivo. For that purpose, we recently developed dedicated image analysis software called Medical Image Analysis Framework (MIAF)-Knee. In this manuscript, our aims are to present current knowledge on CT imaging of the subchondral bone in knee osteoarthritis and to provide a brief introduction to basic technical aspects of MIAF-Knee as well as preliminary results we obtained in patients with knee osteoarthritis as compared to control subjects.

Exercise and fractures in postmenopausal women: 12-year results of the Erlangen Fitness and Osteoporosis Prevention Study (EFOPS).

UNLABELLED: This trial is the first exercise study that focuses on fracture incidence as a primary study endpoint. Although we marginally failed to determine significant effects on "overall" fracture risk (p = .074) or rate ratio (p = .095), our findings further increased the evidence that exercise relevantly prevents fractures in the elderly. INTRODUCTION: The purpose of this study is to determine the effect of strictly supervised long-term exercise training on "overall" fracture incidence and bone mineral density (BMD) in postmenopausal osteopenic women. METHODS: Eighty-five early postmenopausal (1-8 years), osteopenic women living in the area of Erlangen-Nuremberg, Germany without any medication or diseases affecting bone metabolism were assessed after 12 years of supervised exercise (EG) or unvarying lifestyle (control, CG). Exercisers were encouraged to perform two group sessions/week and two home training sessions/week. Calcium and vitamin D supplementation was provided for both groups. "Overall" fractures were determined by questionnaires and structured interviews. The BMD was assessed at lumbar spine and proximal femur by dual-energy X-ray absorptiometry. RESULTS: "Overall" fracture risk ratio in the EG was 0.32 (95% confidence interval (CI), 0.08 to 1.05; p = .074), and the rate ratio for "overall" fractures was 0.38 (95% CI, 0.11 to 1.15; p = .095). BMD changes at lumbar spine (EG, -0.8%; 95% CI, 0.8% to -2.7% vs. CG, -4.0%; 95% CI, -2.4% to -5.7%; p = .011) and femoral neck (EG, -3.7%; 95% CI, -2.4% to -5.0% vs. CG, -6.7%; 95% CI, -5.3% to -8.2%; p = .003) significantly differed between both groups. CONCLUSION: Although we marginally failed to determine significant effects on overall fracture risk or rate ratio, our study increased the body of evidence for the fracture prevention efficiency of exercise programs, with special regard on bone strength (as assessed by bone mineral density measurement). Future studies should focus on subjects more prone to fractures to generate enough statistical power to clearly determine this issue.

An in vivo comparison of hip structure analysis (HSA) with measurements obtained by QCT.

SUMMARY: In a population of elderly women, bone cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), femoral neck axis length (FNAL), and width measured with hip structure analysis (HSA) on dual-energy x-ray absorptiometry (DXA) images in the femoral neck and trochanteric regions are highly correlated to quantitative computed tomography (QCT) measurements. INTRODUCTION: HSA is a method of obtaining measurements of proximal femur structure using 2D DXA technology. This study was designed to examine the correlations between HSA measurements and 3D QCT. METHODS: Forty-one women (mean age, 82.8 ± 2.5 years) were measured using DXA and a 64-slice CT scanner (1 mm slice thickness, 0.29 mm in plane resolution). HSA parameters were calculated at the narrow neck (NN) and trochanteric (IT) regions on the DXA image. These regions were then translated to anatomically equivalent regions on the QCT dataset by co-registering the DXA image and QCT dataset using four DXA images acquired at different angles. RESULTS: At the NN and IT regions, high linear correlations were measured between HSA and QCT for CSA r = 0.95 and 0.93, CSMI r = 0.94 and 0.93, and Z r = 0.93 and 0.89, respectively. All correlations were highly significant (p < 0.001), but there were differences in slope and offset between the two techniques, at least in part due to differences in calibration between the two techniques. FNAL and width of the bone at the NN and IT regions, physical measurements independent of the calibration, were highly correlated (r = 0.90-0.95, p < 0.001) and had slopes close to 1.0 (range, 0.978 to 1.003). CONCLUSION: CSA, CSMI, Z, FNAL, and width measured by HSA correlate highly to high-resolution QCT.

Short-term in vivo precision of BMD and parameters of trabecular architecture at the distal forearm and tibia.

UNLABELLED: In vivo hr-pQCT precision was determined in 42 postmenopausal women using double baseline measurements from a multicenter trial of odanacatib. Errors, e.g., at the radius below 1.3% for BMD and below 6.3% for trabecular structure, were comparable to single-center results. Motion artifacts remain a challenge, particularly at the forearm. INTRODUCTION: The short-term in vivo precision of BMD, trabecular bone structure, cortical thickness and porosity of the forearm and tibia was measured by hr-pQCT. Also the effect of image quality on precision was evaluated. METHODS: In 42 postmenopausal women (age 64.4 ± 6.8 years) out of 214 subjects enrolled in a multi center advanced imaging phase III study of odanacatib (DXA spine or hip T-scores between -1.5 and -3.5), double baseline hr-pQCT (XtremeCT) measurements with repositioning were performed. The standard ultradistal location and a second, more proximally located VOI were measured at the radius and tibia to better assess cortical thickness and porosity. Image analysis and quality grading (grades: perfect, slight artifacts, pronounced artifacts, unacceptable) were performed centrally. RESULTS: At the radius RMS%CV values varied from 0.7% to 1.3% for BMD and BV/TV and from 5.6% to 6.3% for Tb.Sp, Tb.Th, Tb.N, and cortical porosity. Numerically at the tibia, precision errors were approx. 0.5% lower for BMD and 1% to 2% lower for structural parameters although most differences were insignificant. In the radius but not in the tibia, precision errors for cortical thickness were smaller at the distal compared to the ultradistal location (1% versus 2%). CONCLUSIONS: BMD precision errors were lower than those for trabecular architecture and cortical porosity. Motion artifacts remain a challenge, particularly at the forearm. Quality grading remains subjective, and more objective evaluation methods are needed. Precision in the context of a multicenter clinical trial, with centralized training and scan analysis, was comparable to single-center results previously reported.