Reliability and agreement of proton density-weighted vs. gadolinium-enhanced T1-weighted MRI in hand osteoarthritis. An OMERACT MRI special interest group reliability exercise.

OBJECTIVES: To compare reliabilities of assessing synovitis in hand osteoarthritis (OA) using Magnetic Resonance Imaging (MRI) with/without gadolinium (Gd). METHODS: Three readers scored synovitis on non-enhanced two-dimensional (2D) proton density (PD)-weighted MRI and Gd-enhanced (3D) MRI of hand joints in 20 patients. Inter-reader reliabilities were examined. RESULTS: Reliability was good for Gd-enhanced MRI, but poor for non-enhanced PD-weighted MRI (intraclass correlation coefficient 0.83 and 0.21, respectively). Agreement between the two sequences was poor (weighted kappa 0.18). CONCLUSION: Gd-enhanced MRI was more reliable than PD-weighted MRI for assessing synovitis. Gd-enhancement, but also resolution and tissue contrast, might have contributed to this.

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.

Radiological criteria for atypical features of femur fractures: what we can learn when applied in a clinical study setting.

The paper focuses on the identification of atypical fractures (AFFs). This paper examines the concordance between objective classification and expert subjective review. We believe the paper adds critical information about how to apply the American Society of Bone and Mineral Research (ASBMR) criteria to diagnose AFFs and is of high interest to the field. INTRODUCTION: Assess American Society of Bone and Mineral Research (ASBMR) criteria for identifying atypical femoral fractures (AFFs). METHODS: Two orthopedic surgeons independently evaluated radiographs of 372 fractures, applying ASBMR criteria. We assessed ease of applying ASBMR criteria and whether criteria-based assessment matched qualitative expert assessment. RESULTS: There was up to 27% uncertainty about how to classify specific features. 84% of films were classified similarly for the presence of AFF according to ASBMR criteria; agreement increased to 94% after consensus meeting. Of 37 fractures categorized as AFFs based on ASBMR criteria, 23 (62.2%) were considered AFFs according to expert assessment (not relying on criteria). Only one (0.5%) femoral shaft fracture that did not meet ASBMR criteria was considered an AFF per expert assessment. The number of major ASBMR features present (four vs five) and whether there was periosteal or endosteal thickening ("beaking" or "flaring") played major roles in the discrepancies between ASBMR criteria-based and expert-based determinations. CONCLUSIONS: ASBMR AFF criteria were useful for reviewers but several features were difficult to interpret. Expert assessments did not agree with the ASBMR classification in almost one-third of cases, but rarely identified an AFF when a femoral shaft fracture did not meet ASBMR AFF criteria. Experts identified lateral cortical transverse fracture line and associated new-bone formation along with no or minimal comminution as crucial features necessary for the definition of atypical femoral fractures.

Automated quantitative morphometry of vertebral heights on spinal radiographs: comparison of a clinical workflow tool with standard 6-point morphometry.

A workflow tool for measurements of vertebral heights on lateral spine radiographs based on automated placements of 6 points per vertebra was evaluated. The tool helps to standardize point placement among operators. Its success rate is very good in normal vertebrae but lower in vertebrae with more severe fractures. Manual corrections were required in 192 of 1257 analyzed vertebrae. INTRODUCTION: To evaluate a new workflow tool (SA) for the automated measurements of vertebral heights on lateral spine radiographs. METHODOLOGY: Lateral radiographs from 200 postmenopausal women were evaluated at two visits. Genant's semi-quantitative fracture assessment (SQ) and manual quantitative morphometry (QM) results were available from prior analyses. Vertebral heights from point placements using SA were compared with manual 6-point placement QM. Differences were quantified as RMS coefficient of variations (rmsCV) and standard deviations (rmsSD). RESULTS AND CONCLUSIONS: SA required manual corrections in 192 of 1257 vertebrae. SA heights were larger than QM ones by 2.2-3.6%. Correlations (r2 > 0.92) between SA and QM were very high. Differences between QM and SA were higher for fractured (SQ = 2; rmsCV% 14.5%) than for unfractured vertebrae (rmsCV% 4.2-4.7%). rmsCV% for QM varied between 3 and 6% and for SA between 2.5 and 7.5%. For SA, highest rmsCV% was obtained for T4 and L4. Manual correction mostly affected the end vertebrae T4 and L4. SA helps to standardize point placement among operators. The algorithm success rate is very good in normal vertebrae but lower in vertebrae with more severe fractures, which are of greater clinical interest but are more readily recognized without morphometric measurements.

Spine fracture prevalence in a nationally representative sample of US women and men aged ≥40 years: results from the National Health and Nutrition Examination Survey (NHANES) 2013-2014.

Spine fracture prevalence is similar in men and women, increasing from <5 % in those <60 to 11 % in those 70-79 and 18 % in those ≥80 years. Prevalence was higher with age, lower bone mineral density (BMD), and in those meeting criteria for spine imaging. Most subjects with spine fractures were unaware of them. INTRODUCTION: Spine fractures have substantial medical significance but are seldom recognized. This study collected contemporary nationally representative spine fracture prevalence data. METHODS: Cross-sectional analysis of 3330 US adults aged ≥40 years participating in NHANES 2013-2014 with evaluable Vertebral Fracture Assessment (VFA). VFA was graded by semiquantitative measurement. BMD and an osteoporosis questionnaire were collected. RESULTS: Overall spine fracture prevalence was 5.4 % and similar in men and women. Prevalence increased with age from <5 % in those <60 to 11 % in those 70-79 and 18 % in those ≥80 years. Fractures were more common in non-Hispanic whites and in people with lower body mass index and BMD. Among subjects with spine fracture, 26 % met BMD criteria for osteoporosis. Prevalence was higher in subjects who met National Osteoporosis Foundation (NOF) criteria for spine imaging (14 vs 4.7 %, P < 0.001). Only 8 % of people with a spine fracture diagnosed by VFA had a self-reported fracture, and among those who self-reported a spine fracture, only 21 % were diagnosed with fracture by VFA. CONCLUSION: Spine fracture prevalence is similar in women and men and increases with age and lower BMD, although most subjects with spine fracture do not meet BMD criteria for osteoporosis. Since most (>90 %) individuals were unaware of their spine fractures, lateral spine imaging is needed to identify these women and men. Spine fracture prevalence was threefold higher in individuals meeting NOF criteria for spine imaging (∼1 in 7 undergoing VFA). Identifying spine fractures as part of comprehensive risk assessment may improve clinical decision making.

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.

The first multicenter and randomized clinical trial of herbal Fufang for treatment of postmenopausal osteoporosis.

UNLABELLED: This multicenter and randomized clinical trial showed that daily oral herbal formula Xian Ling Gu Bao (XLGB) was safe in postmenopausal women over a 1-year treatment. Those patients (n ∼ 50) treated with XLGB at the conventional dose demonstrated a statistically significant increase in dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) at lumbar spine at 6 months and a numerically increased BMD at 12 months. INTRODUCTION: The aim of this study was to examine the safety and efficacy of a herbal formula XLGB in postmenopausal women (ChiCTR-TRC-00000347). METHODS: One hundred eighty healthy postmenopausal women (≥60 years old) with BMD T-score ≤ -2.0 (lumbar spine or femoral neck) were recruited from four clinical centers to receive low-dose (conventional dose) XLGB (L-XLGB group, 3 g/day, n = 61) or high-dose XLGB (H-XLGB group, 6 g/day, n = 58) or placebo (CON group, n = 61). Women received daily calcium (500 mg) and vitamin D (200 IU) supplementation. Primary endpoints were lumbar spine BMD and safety; secondary endpoints were femoral neck BMD and bone turnover markers measured at baseline and at 6 and 12 months. RESULTS: Of 180 women recruited, 148 completed the study. The compliance in each group was comparable. Prominent adverse events were not observed in either group. In the L-XLGB group at 6 months, lumbar spine BMD by DXA increased significantly from baseline (+2.11% versus CON +0.58%, p < 0.05), but femoral neck BMD did not; at 12 months, BMD in the L-XLGB group decreased from 6-month levels yet remained higher than baseline, but without difference from the CON group. There was no dose-dependent response. Bone turnover marker levels declined during the first 6 months after XLGB treatment. There was no significant difference in the overall incidence of side effects among treatment and control groups. CONCLUSION: XLGB over 1-year treatment at the conventional dose demonstrated safe and only a statistically significant increase in BMD at lumbar spine at 6 months in postmenopausal women.

Identification of prevalent vertebral fractures using CT lateral scout views: a comparison of semi-automated quantitative vertebral morphometry and radiologist semi-quantitative grading.

UNLABELLED: We compared vertebral fracture assessment by semi-automated quantitative vertebral morphometry measurements with the conventional semi-quantitative (SQ) grading using lateral CT scout views. The semi-automated morphometry method showed good to excellent agreement with the visual SQ grading by radiologists for identification of vertebral fractures. INTRODUCTION: Semi-automated quantitative vertebral morphometry (QM) measurements may enhance management of osteoporosis patients by providing an efficient means to identify vertebral fractures (VFx). We compared identification of prevalent VFx by semi-automated QM to SQ grading. METHODS: A non-radiologist performed semi-automated QM from CT lateral scout views in 200 subjects (102 men, 98 women, 65.8 ± 8.9 years) selected from the Framingham Heart Study Multidetector CT Study. VFx were classified in the QM approach based on using Genant's criteria for deformities, and compared with conventional SQ grading performed by experienced radiologists as the gold standard. The kappa (k) statistics, percent agreement (% Agree), sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) were computed. RESULTS: Among 200 subjects, 57 had mild and 41 had moderate or severe VFx by visual SQ grading. Per-person analyses showed excellent agreement between the two methods, with k = 0.780. The % Agree ranged from 86.7% to 91.2%, the SE was 81.3%-96%, and the SP was 86.5%-92%. Among 2,588 vertebrae analyzed, 107 had mild and 49 had moderate or severe VFx by visual SQ grading. Per-vertebra analyses revealed good agreement, with k = 0.580. Agreement between the methods tended to be highest in L1-L4 region. Agreement and validity measures were higher when only moderate and severe fractures were included. CONCLUSION: The semi-automated quantitative vertebral morphometry measurements from CT lateral scout views provided good to excellent agreement with the standard SQ grading for assessment of prevalent vertebral fractures.

Effect of monthly ibandronate on hip structural geometry in men with low bone density.

UNLABELLED: Hip structural analysis (HSA) performed in a subset of participants from the STudy Researching Osteoporosis iN Guys (STRONG) demonstrated that 1 year of ibandronate treatment was associated with a significant improvement in some but not all parameters of hip geometry relative to placebo in men with low bone density. INTRODUCTION: HSA was performed on dual-energy X-ray absorptiometry (DXA) images in a subset of participants from the STRONG to examine the impact of monthly ibandronate on geometric properties of the hip in men with low bone density. METHODS: This prespecified subgroup analysis evaluated men in the intent-to-treat population of STRONG with baseline and 12-month DXA data. Cross-sectional geometric parameters of the femoral shaft (FS), intertrochanter region (IT), and narrow neck (NN) were calculated from femoral DXA scans. All analyses were exploratory. Treatment differences were evaluated using analysis of covariance, which adjusted for baseline parameter value, testosterone level, and treatment. RESULTS: HSA was performed on DXA scans from 89 men (34 placebo; 55 monthly ibandronate). Significant increases in average cortical thickness and cross-sectional area and decreases (i.e., improvements) in the buckling ratio were observed at the FS and IT at 12 months for ibandronate-treated men compared with placebo-treated men. No significant differences were observed between ibandronate and placebo for any NN HSA parameters. CONCLUSIONS: One year of ibandronate treatment was associated with a significant improvement in some but not all parameters of hip geometry relative to placebo in men with low bone density, suggesting that ibandronate may improve resistance to axial compressive forces and bending forces at the hip.

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.

Reliability of vertebral fracture assessment using multidetector CT lateral scout views: the Framingham Osteoporosis Study.

UNLABELLED: Two radiologists evaluated images of the spine from computed tomography (CT) scans on two occasions to diagnose vertebral fracture in 100 individuals. Agreement was fair to good for mild fractures, and agreement was good to excellent for more severe fractures. CT scout views are useful to assess vertebral fracture. INTRODUCTION: We investigated inter-reader agreement between two radiologists and intra-reader agreement between duplicate readings for each radiologist, in assessment of vertebral fracture using a semi-quantitative method from lateral scout views obtained by CT. METHODS: Participants included 50 women and 50 men (age 50-87 years, mean 70 years) in the Framingham Study. T4-L4 vertebrae were assessed independently by two radiologists on two occasions using a semi-quantitative scale as normal, mild, moderate, or severe fracture. RESULTS: Vertebra-specific prevalence of grade ≥ 1 (mild) fracture ranged from 3% to 5%. We found fair (κ = 56-59%) inter-reader agreement for grade ≥ 1 vertebral fractures and good (κ = 68-72%) inter-reader agreement for grade ≥ 2 fractures. Intra-reader agreement for grade ≥ 1 vertebral fracture was fair (κ = 55%) for one reader and excellent for another reader (κ = 77%), whereas intra-reader agreement for grade ≥ 2 vertebral fracture was excellent for both readers (κ = 76% and 98%). Thoracic vertebrae were more difficult to evaluate than the lumbar region, and agreement was lowest (inter-reader κ = 43%) for fracture at the upper (T4-T9) thoracic levels and highest (inter-reader κ = 76-78%) for the lumbar spine (L1-L4). CONCLUSIONS: Based on a semi-quantitative method to classify vertebral fractures using CT scout views, agreement within and between readers was fair to good, with the greatest source of variation occurring for fractures of mild severity and for the upper thoracic region. Agreement was good to excellent for fractures of at least moderate severity. Lateral CT scout views can be useful in clinical research settings to assess vertebral fracture.

Vertebral fracture risk (VFR) score for fracture prediction in postmenopausal women.

SUMMARY: Early prognosis of osteoporosis risk is not only important to individual patients but is also a key factor when screening for osteoporosis drug trial populations. We present an osteoporosis fracture risk score based on vertebral heights. The score separated individuals who sustained fractures (by follow-up after 6.3 years) from healthy controls at baseline. INTRODUCTION: This case-control study was designed to assess the ability of three novel fracture risk scoring methods to predict first incident lumbar vertebral fractures in postmenopausal women matched for classical risk factors such as BMD, BMI, and age. METHODS: This was a case-control study of 126 postmenopausal women, 25 of whom sustained at least one incident lumbar fracture and 101 controls that maintained skeletal integrity over a 6.3-year period. Three methods for fracture risk assessment were developed and tested. They are based on anterior, middle, and posterior vertebral heights measured from vertebrae T12-L5 in lumbar radiographs at baseline. Each score's fracture prediction potential was investigated in two variants using (1) measurements from the single most deformed vertebra or (2) average measurements across vertebrae T12-L5. Emphasis was given to the vertebral fracture risk (VFR) score. RESULTS: All scoring methods demonstrated significant separation of cases from controls at baseline. Specifically, for the VFR score, cases and controls were significantly different (0.67 ± 0.04 vs. 0.35 ± 0.03, p < 10 (-6)) with an AUC of 0.82. Dividing the VFR scores into tertiles, the fracture odds ratio for the highest versus lowest tertile was 35 (p < 0.001). Sorting the combined case-control group according to VFR score resulted in 90% of cases in the top half. CONCLUSION: At baseline, the three scores separated cases from controls and, especially, the VFR score appears to be predictive of fractures. Control experiments, however also, indicate that VFR-based fracture prediction is operator/annotator dependent and high-quality annotations are needed for good fracture prediction.

Denosumab improves density and strength parameters as measured by QCT of the radius in postmenopausal women with low bone mineral density.

BACKGROUND: Bone strength is determined by both cortical and trabecular bone compartments and can be evaluated radiologically through measurement of bone density and geometry. Quantitative computed tomography (QCT) separately assesses cortical and trabecular bone reliably at various sites, including the distal radius where there is a gradation of cortical and trabecular bone. We evaluated the effect of denosumab, a fully human monoclonal antibody that inhibits RANK ligand, on distal radius QCT in women with low bone mass to assess the impact of this novel therapy separately on trabecular and cortical bone. METHODS: Postmenopausal women (n=332) with spine areal bone mineral density (BMD) T-scores between -1.0 and -2.5 received denosumab 60 mg or placebo every 6 months during the 24-month study. QCT measurements along the distal radius were made using a whole-body computed tomography scanner and were used to determine the percentage change from baseline in volumetric BMD; volumetric bone mineral content (BMC); cortical thickness; volume; circumference; and density-weighted polar moment of inertia (PMI), a derived index of bone strength. RESULTS: Denosumab treatment significantly increased total BMD and BMC along the radius (proximal, distal, and ultradistal sections). At 24 months, the ultradistal region had the greatest percentage increase in total BMD (4.7% [95% CI, 3.6-5.7]; P<0.001) and total BMC (5.7% [95% CI, 4.8-6.6]; P<0.001) over placebo. When cortical and trabecular bone at the proximal and distal regions were separately assessed, cortical bone had significant (P<0.001) increases in BMD, BMC, and thickness, and trabecular bone had a significant increase in BMD relative to placebo (P<0.05). Bone strength, estimated by density-weighted PMI, significantly increased compared with placebo after 6 months of treatment, with the largest percentage increase occurring at 24 months in the ultradistal region (6.6% [95% CI, 5.6-7.6]; P<0.0001). CONCLUSIONS: QCT measurements demonstrated that denosumab significantly increased BMD, BMC, and PMI along the radius over 24 months. Additionally, denosumab prevented the decrease in QCT-measured cortical thickness observed in the placebo group. These data extend the evidence from previous dual-energy X-ray absorptiometry studies for a positive effect of denosumab on both the cortical and trabecular bone compartments and propose a possible mechanism for the reduction in fracture risk achieved with denosumab therapy.

Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial).

BACKGROUND: Several agents provide treatment for established rheumatoid arthritis (RA), but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA. OBJECTIVE: To determine the impact of T-cell costimulation modulation in patients with UA or very early RA. METHODS: In this double-blind, phase II, placebocontrolled, 2-year study, anti-cyclic citrullinated peptide (CCP)2-positive patients with UA (not fulfilling the ACR criteria for RA) and clinical synovitis of two or more joints were randomised to abatacept ( approximately 10 mg/kg) or placebo for 6 months; the study drug was then terminated. The primary end point was development of RA (by ACR criteria) at year 1. Patients were monitored by radiography, MRI, CCP2, rheumatoid factor and 28 joint count Disease Activity Score (DAS28) over 2 years. RESULTS: At year 1, 12/26 (46%) abatacept-treated versus 16/24 (67%) placebo-treated patients developed RA (difference (95% CI) -20.5% (-47.4% to 7.8%)). Adjusted mean changes from baseline to year 1 in Genant-modified Sharp radiographic scores for abatacepttreated versus placebo-treated patients, respectively, were 0 versus 1.1 for total score, and 0 versus 0.9 for erosion score. Mean changes from baseline to year 1 in MRI erosion, osteitis and synovitis scores were 0, 0.2 and 0.2, respectively, versus 5.0, 6.7 and 2.3 in the abatacept versus placebo groups. Safety was comparable between groups; serious adverse events occurred in one patient (3.6%) in each group. CONCLUSION: Abatacept delayed progression of UA/very early RA in some patients. An impact on radiographic and MRI inhibition was seen, which was maintained for 6 months after treatment stopped. This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease. Trial registration number NCT00124449.

Vertebral fracture assessment: impact of instrument and reader.

PURPOSE: Many osteoporotic vertebral fractures are not clinically recognized but increase fracture risk. We hypothesized that a newer generation densitometer increases the number of evaluable vertebrae and vertebral fractures detected. We also explored the impact of reader experience on vertebral fracture assessment (VFA) interpretation. METHODS: VFA images obtained using Prodigy and iDXA densitometers in 103 older adults were evaluated for vertebral visualization and fracture presence in the T4-L5 region. A "true" read for each densitometer was achieved by consensus. If readers disagreed, the evaluation of a third expert physician was taken as true. Main outcomes were evaluable vertebrae, vertebral fractures, and intrareader/interreader reproducibility. RESULTS: Using the "true" reads, 92% of vertebrae were visualized on iDXA and 76% on Prodigy. Numerically, more fractures were identified with iDXA; the "true" reads found 43 fractures on iDXA and 21 on Prodigy. The experienced reader had better intrareader and interreader reproducibility than the inexperienced reader when compared with the "true" read. CONCLUSIONS: Using the newer iDXA densitometer for VFA analysis improves vertebral body visualization and fracture detection. Training and experience enhance result reproducibility.

Evaluation of vertebral fracture assessment by dual X-ray absorptiometry in a multicenter setting.

SUMMARY: The utility of vertebral fracture assessment (VFA) by DXA to detect prevalent vertebral fracture in a multicenter setting was investigated by comparison to conventional radiography. While limited by lower image quality, overall performance of VFA was good but had a tendency to miss mild prevalent fractures. INTRODUCTION: In osteoporosis clinical trials standardized spine radiographs are used to detect vertebral fractures as a study endpoint. Lateral spine imaging with dual X-ray absorptiometry (DXA) scanners, known as vertebral fracture assessment (VFA) by DXA, presents a potential alternative to conventional radiography with lower radiation dose and greater patient convenience. METHODS: We investigated in a multicenter setting the ability of VFA to detect fractures in comparison with conventional radiography. The study examined 203 postmenopausal women who had imaging of the spine by DXA and radiography. Three radiologists experienced in vertebral fracture assessment independently read the VFA scans and radiographs using the Genant semiquantitative method on two occasions. CONCLUSIONS: Analyzing the data from all readable vertebrae, the kappa statistic, sensitivity, and specificity ranged from 0.64-0.77, 0.65-0.84, and 0.97-0.98, respectively. Considering only moderate and severe fractures improved the kappa statistic (0.80-0.91) and sensitivity (0.70-0.86). While image quality of VFA is inferior to radiography, the detection of vertebral fractures using visual scoring is feasible. However, VFA underperformed due to unreadable vertebrae and reduced sensitivity for mild fractures. Nevertheless, VFA correctly identified most moderate and severe vertebral fractures. Despite this limitation, VFA by DXA provides an important tool for clinical research.

Advanced CT bone imaging in osteoporosis.

Non-invasive and/or non-destructive techniques can provide structural information about bone, beyond simple bone densitometry. While the latter provides important information about osteoporotic fracture risk, many studies indicate that BMD only partly explains bone strength. Quantitative assessment of macro- and microstructural features may improve our ability to estimate bone strength. Methods for quantitatively assessing macrostructure include (besides conventional radiographs) DXA and CT, particularly volumetric quantitative CT (vQCT). Methods for assessing microstructure of trabecular bone non-invasively and/or non-destructively include high-resolution CT (hrCT), microCT (microCT), high-resolution magnetic resonance (hrMR) and microMR (microMR). vQCT, hrCT and hrMR are generally applicable in vivo; microCT and microMR are principally applicable in vitro. Despite recent progress made with these advanced imaging techniques, certain issues remain. The important balances between spatial resolution and sampling size, or between signal-to-noise and radiation dose or acquisition time, need further consideration, as do the complexity and expense of the methods vs their availability and accessibility. Clinically, the challenges for bone imaging include balancing the advantages of simple bone densitometry vs the more complex architectural features of bone or the deeper research requirements vs the broader clinical needs. The biological differences between the peripheral appendicular skeleton and the central axial skeleton must be further addressed. Finally, the relative merits of these sophisticated imaging techniques must be weighed with respect to their applications as diagnostic procedures, requiring high accuracy or reliability, compared with their monitoring applications, requiring high precision or reproducibility.

Improved precision with Hologic Apex software.

UNLABELLED: The precision of Hologic Apex v2.0 analysis software is significantly improved from Hologic Delphi v11.2 software and is comparable to GE Lunar Prodigy v7.5 software. Apex and Delphi precisions were, respectively, 1.0% vs. 1.2% (L1-L4 spine), 1.l % vs. 1.3% (total femur), 1.6% vs. 1.9% (femoral neck), and 0.7% vs. 0.9% (dual total femur). INTRODUCTION: Precision of bone mineral density (BMD) measurements by dual-energy X-ray absorptiometry (DXA) is known to vary by manufacturer, model, and technologist. This study evaluated the precision of three analysis versions: Apex v2.0 and Delphi v11.2 (Hologic, Inc.), and Prodigy v7.5 (GE Healthcare, Inc.) independent of technologist skill. METHODS: Duplicate spine and dual hip scans on 90 women were acquired on both Delphi and Prodigy DXA systems at three clinics. BMD measures were converted to standardized BMD (sBMD) units. Precision errors were described as a root-mean-square (RMS) standard deviations and RMS percent coefficients of variation across the population. RESULTS: Apex and Delphi values were highly correlated (r ranged from 0.90 to 0.99). Excluding the right neck, the Apex precision error was found to be 20% to 25% lower than the Delphi (spine: 1.0% versus 1.2% (p < 0.05), total hip: 1.1% versus 1.3% (p < 0.05), right neck: 2.3% versus 2.6% (p > 0.1)). No statistically significant differences were found in the precision error of the Apex and Prodigy (p > 0.05) except for the right neck (2.3% versus 1.8% respectively, p = 0.03). CONCLUSION: The Apex software has significantly lower precision error compared to Delphi software with similar mean values, and similar precision to that of the Prodigy.

Abatacept inhibits progression of structural damage in rheumatoid arthritis: results from the long-term extension of the AIM trial.

OBJECTIVE: Assess the effect of abatacept on progression of structural damage over 2 years in patients with rheumatoid arthritis who had an inadequate response to methotrexate. METHODS: 539 patients entered an open-label extension of the AIM (Abatacept in Inadequate responders to Methotrexate) trial and received abatacept. Radiographic assessment of the hands and feet was performed at baseline, year 1 and year 2. At year 2, each patient's radiographs were scored for progression blinded to sequence and treatment allocation. RESULTS: In patients treated with abatacept for 2 years, greater reduction in progression of structural damage was observed in year 2 than in year 1. The mean change in total Genant-modified Sharp scores was reduced from 1.07 units in year 1 to 0.46 units in year 2. Similar reductions were observed in erosion and joint space narrowing scores. Following 2 years of treatment with abatacept, 50% of patients had no progression of structural damage as defined by a change in the total score of < or =0 compared with baseline. 56% of patients treated with abatacept had no progression during the first year compared with 45% of patients treated with placebo. In their second year of treatment with abatacept, more patients had no progression than in the first year (66% vs 56%). CONCLUSIONS: Abatacept has a sustained effect that inhibits progression of structural damage. Furthermore, the mean change in radiographic progression in patients treated with abatacept for 2 years was significantly lower in year 2 versus year 1, suggesting that abatacept may have an increasing disease-modifying effect on structural damage over time.

Meniscal damage associated with increased local subchondral bone mineral density: a Framingham study.

OBJECTIVE: Because menisci and the medial vs lateral tibial plateau bone mineral density ratio (M:L BMD) are associated with loading within the knee, we postulated there to be an association between compartment-specific meniscal damage and M:L BMD. We hypothesized that knees with higher M:L BMD, consistent with increased medial subchondral BMD, would be associated with medial meniscal damage, and lower ratios with lateral meniscal damage. METHODS: We conducted a cross-sectional study evaluating participants in the Framingham Osteoarthritis Cohort having magnetic resonance images (MRIs), BMDs, and x-rays of the knee. Medial and lateral meniscal damage were defined on MRI. We performed a logistic regression with medial meniscal damage as the outcome testing M:L BMD groups as predictor variables. We adjusted for age and sex; we used generalized estimating equations (GEE) to adjust for correlation between knees. Identical analyses were performed evaluating lateral meniscal damage. RESULTS: When evaluating the relation of M:L BMD to medial meniscal damage, the odds ratios (ORs) of prevalent medial meniscal damage from lowest to highest quartile of M:L BMD were 1.0 (referent), 1.9, 2.4 and 8.9, P for trend <0.0001. When evaluating the relation of M:L BMD to lateral meniscal damage, the ORs of prevalent lateral meniscal damage from lowest to highest quartile of M:L BMD were 1.0 (referent), 0.3, 0.2, and 0.2, P for trend = 0.001. CONCLUSIONS: Meniscal damage is associated with higher regional tibial BMD in the same compartment. Our findings highlight the close relationship between meniscal integrity and regional tibial subchondral BMD.