Characterizing Osteophyte Formation in Knee Osteoarthritis: Application of Machine Learning Quantification of a Computerized Tomography Cohort: Implications for Treatment.

BACKGROUND: Osteophytes are commonly used to diagnose and guide knee osteoarthritis (OA) treatment, but their causes are unclear. Although they are not typically the focus of knee arthroplasty surgeons, they can predict case difficulty and length. Furthermore, their extent and location may yield much information about the knee joint status. The aims of this computed tomography-based study in patients awaiting total or partial knee arthroplasty were to: (1) measure osteophyte volume in anatomical subregions and relative change as total volume increases; (2) determine whether medial and/or lateral OA affects osteophyte distribution; and (3) explore relationships between osteophytes and OA severity. METHODS: Data were obtained from 4,928 computed tomography scans. Machine-learning-based imaging analyses enabled osteophyte segmentation and quantification, divided into anatomical regions. Mean three-dimensional joint space narrowing was assessed in medial and lateral compartments. A Bayesian model assessed the uniformity of osteophyte distribution. We correlated femoral osteophyte volumes with B-scores, a validated OA status measure. RESULTS: Total tibial (25%) and femoral osteophyte volumes (75%) within each knee correlated strongly (R2 = 0.85). Medial osteophytes (65.3%) were larger than lateral osteophytes (34.6%), with similar proportions in both the femur and tibia. Osteophyte growth was found in all compartments, and as total osteophyte volume increased, the relative distribution of osteophytes between compartments did not markedly change. No evidence of variation was found in the regional distribution of osteophyte volume between knees with medial, lateral, both, or no three-dimensional joint space narrowing in the femur or tibia. There was a direct relationship between osteophyte volume and OA severity. CONCLUSIONS: Osteophyte volume increased in both medial and lateral compartments proportionally with total osteophyte volume, regardless of OA location. The peripheral position of femoral osteophytes does not appear to contribute to load-bearing. This suggests that osteophytic growth represents a 'whole-knee'/global response. This work may have broad applications for knee OA, both surgically and nonoperatively.

Using 3D MRI Bone Shape to Predict Pre-Osteoarthritis of the Knee 2 Years After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Anterior cruciate ligament (ACL) injury increases risks for osteoarthritis (OA), a poorly modifiable and disabling condition. Joint changes of potentially reversible pre-OA have been described just 2 years after ACL reconstruction (ACLR) when early bone shape changes have also been reported. PURPOSE: This study evaluates relationships between interlimb differences in tibiofemoral bone shape derived from statistical shape modeling (SSM) of magnetic resonance imaging (MRI) and participant factors on patient-reported outcomes 2 years after unilateral ACLR. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: SSM-derived tibiofemoral bone shape and subchondral bone area were assessed from bilateral knee MRI scans of 72 participants with unilateral ACLR (mean age, 34 ± 11 years; 32 women) and compared with a reference cohort of 398 older individuals without OA (mean age, 50 ± 3 years; 213 women). Multivariable logistic regression models examined relationships between participant and surgical factors with interlimb differences in bone shapes or subchondral bone areas. Relationships between patient-reported outcomes and the interlimb differences in bone shape and subchondral area were examined using similar models. RESULTS: Bone shape scores and subchondral bone areas were greater (more OA-like) in ACLR knees than uninjured contralateral knees in every bone metric tested (P≤ .001). Interlimb differences in femur shape scores of participants with ACLR were 65% greater (P < .001) than those of the significantly older reference cohort. Taller height, medial meniscal tears, and decreasing age were associated with larger interlimb differences in shape scores and subchondral areas (P < .05). Bone-patellar tendon-bone (BPTB) autograft recipients demonstrated greater interlimb subchondral area differences compared with allograft recipients (P < .05). Interlimb differences for hamstring autograft recipients did not differ from those with BPTB or allograft. Greater interlimb differences in medial femur subchondral areas were associated with worse patient-reported Knee injury and Osteoarthritis Outcome Score Symptoms (R = 0.27; P = .040). CONCLUSION: Even in the absence of radiographic OA, just 2 years after unilateral ACLR patients showed greater bone shape scores and subchondral areas consistent with pre-OA in their ACLR knees. Furthermore, greater medial femur bone areas were weakly associated with worse symptoms. Patients who are younger, are taller, have meniscal tears, or have BPTB grafts may be at increased risk for bony asymmetries 2 years after ACLR.

Comparison of 3D quantitative osteoarthritis imaging biomarkers from paired CT and MR images: data from the IMI-APPROACH study.

INTRODUCTION: MRI bone surface area and femoral bone shape (B-score) measures have been employed as quantitative endpoints in DMOAD clinical trials. Computerized Tomography (CT) imaging is more commonly used for 3D visualization of bony anatomy due to its high bone-soft tissue contrast. We aimed to compare CT and MRI assessments of 3D imaging biomarkers. METHODS: We used baseline and 24-month image data from the IMI-APPROACH 2-year prospective cohort study. Femur and tibia were automatically segmented using active appearance models, a machine-learning method, to measure 3D bone shape, area and 3D joint space width (3DJSW). Linear regression was used to test for correlation between measures. Limits of agreement and bias were tested using Bland-Altman analysis. RESULTS: CT-MR pairs of the same knee were available from 434 participants (78% female). B-scores from CT and MR were strongly correlated (CCC = 0.967) with minimal bias of 0.1 (SDD = 0.227). Area measures were also correlated but showed a consistent bias (MR smaller). 3DJSW showed different biases (MR larger) in both lateral and medial compartments. DISCUSSION: The strong correlation and small B-score bias suggests that B-score may be measured reliably using either modality. It is likely that the bone surface identified using MR and CT will be at slightly different positions within the bone/cartilage boundary. The negative bone area bias suggests the MR bone boundary is inside the CT boundary producing smaller areas for MR, consistent with the positive 3DJSW bias. The lateral-medial 3DJSW difference is possibly due to a difference in knee pose during acquisition (extended for CT, flexed for MR). TRIAL REGISTRATION: NCT03883568.

New types of investments needed to address barriers to scaling up wildfire risk mitigation.

Background: Wildfire mitigation is becoming increasingly urgent, but despite the availability of mitigation tools, such as prescribed fire, managed wildfire, and mechanical thinning, the USA has been unable to scale up mitigation. Limited agency capacity, inability to work across jurisdictions, lack of public support, and procedural delays have all been cited as barriers to mitigation. But in the context of limited resources and increasing urgency, how should agencies prioritize investments to address these barriers? Results: To better understand different investments for scaling up mitigation, we examined how the wildfire problem is framed, building on existing social science demonstrating that agency approaches depend in part on how problems are framed. Using national-level policy documents and in-depth interviews, we found three ways of framing the barriers to scaling up mitigation, each emphasizing certain aspects of the problem and prioritizing different solutions or investments. The first framing, the Usual Suspects, focused on inadequate resources, cumbersome procedural requirements, delays due to litigation, and lack of public support. The solutions-to increase funding, streamline NEPA, limit litigation, and educate the public-suggest that more resources and fewer restrictions will enable agencies to scale up mitigation. The second framing, Agency-Agency Partnerships, focused on the ways that organizational structure and capacity constrain the development of effective cross-boundary collaboration. Here solutions prioritized organizational changes and capacity building to enable agencies to navigate different missions and build trust in order to develop shared priorities. The third framing, Engaging the Public, focused on lack of public support for mitigation, the need for meaningful public engagement and multi-stakeholder collaboration, and investments to build support to scale up mitigation. Conclusions: This analysis reveals that investing in collaborative capacity to advance agency-agency partnerships and public engagement might not slow down mitigation, but rather enable agencies to "go slow to go fast" by building the support and mechanisms necessary to increase the pace and scale of mitigation work. Reframing the wildfire problem through a careful analysis of competing frames and the underlying assumptions that privilege particular solutions can reveal a broader suite of solutions that address the range of key barriers.

Antecedentes: La mitigación de incendios es una tarea urgente, aunque a pesar de la disponibilidad de herramientas de mitigación, tales como quemas prescriptas, manejo del fuego, y raleos mecánicos, EEUU no ha sido aún capaz de aumentar proporcionalmente la mitigación de sus incendios. Las limitaciones en las capacidades de las agencias, la inhabilidad de trabajar entre jurisdicciones, la falta de apoyo de la sociedad, y demoras en los procedimientos, han sido citados como barreras para la mitigación. Ahora bien, en el contexto de recursos limitados e incrementos en las urgencias, ¿cómo deberían las agencias priorizar las inversiones para enfrentar esas barreras? Resultados: Para entender mejor las distintas inversiones para aumentar proporcionalmente las tareas de mitigación, examinamos cómo el problema de los incendios es enmarcado y construido en la ciencia social existente, demostrando que los enfoques de las agencias dependen, en parte, en cómo esos problemas son abordados. Usando documentos de políticas públicas y entrevistas profundas e intuitivas, encontramos tres vías de enmarcar las barreras para aumentar proporcionalmente la mitigación, cada una enfocando ciertos aspectos del problema y priorizando diferentes soluciones o inversiones. El primer enfoque, las "Sospechas Habituales", estuvo orientado hacia la inadecuación de los recursos, procedimientos incómodos, demoras debidas a litigios, y la falta de respaldo público. Las soluciones -incrementar los recursos, simplificar los procedimientos de la ley ambiental, limitar los litigios, y educar al público- sugieren que más recursos y menos restricciones permitirán a las agencias aumentar proporcionalmente la mitigación. El segundo enfoque "Asociación Agencia-Agencia", se orientó en la forma en que la estructura organizacional y su capacidad condicionan el desarrollo de una colaboración efectiva entre agencias. La solución aquí prioriza los cambios organizacionales y la capacidad de construcción para permitir a las agencias acometer diferentes misiones y crear confianza para poder desarrollar prioridades compartidas. El tercer enfoque "Comprometer al Público" se enfoca en la falta de apoyo del público para la mitigación, y la necesidad de atraer al público y la colaboración de diferentes ciudadanos interesados, en realizar aportes necesarios para construir aportes para el desarrollo de prioridades de mitigación. Conclusiones: Este análisis revela que la inversión en capacidad colaborativa para avanzar en la asociación agencia-agencia y el compromiso público puede no reducir la mitigación, más sin embargo permitir a las agencias "ir despacio para ir más rápido" para construir el soporte y mecanismos necesarios para incrementar la velocidad y la escala del trabajo de mitigación. Reencuadrar el problema de los incendios forestales a través de un cuidadoso análisis de encajes competitivos y suposiciones subyacentes que privilegie soluciones particulares, puede revelar un más amplio conjunto de soluciones que atienda el rango de barreras claves.

Study TPX-100-5: intra-articular TPX-100 significantly delays pathological bone shape change and stabilizes cartilage in moderate to severe bilateral knee OA.

BACKGROUND: TPX-100, a promotor of osteoblast and chondroblast differentiation, is a potential osteoarthritis (OA) therapy. This retrospective study compared MRI 3D femoral bone shape changes (B-scores) after intra-articular TPX-100 or placebo and analyzed the relationship between cartilage thickness and bone shape change over 12 months. METHODS: One hundred and four participants with bilateral moderate to severe knee cartilage defects were randomized to receive TPX-100 (200 mg) or placebo. Each subject's contralateral placebo-treated knee served as a paired internal control. After MRI quality control, 78/93 subjects (84%; 156 knees) were analyzed for quantitative femoral B-score and cartilage thickness. All analyses were performed centrally, blind to treatment assignment and clinical data. RESULTS: TPX-100-treated knees (n = 78) demonstrated a statistically significant decrease in pathologic bone shape change compared with placebo-treated knees at 6 and 12 months: 0.0298 (95% C.I. - 0.037, 0.097) vs 0.1246 (95% C.I. 0.067, 0.182) (P = 0.02), and 0.0856 (95% C.I. 0.013, 0.158) vs. 0.1969 (95% C.I. 0.123, 0.271) (P = 0.01), respectively. The correlation between bone shape change and medial and total tibiofemoral cartilage thickness changes at 12 months was statistically significant in TPX-100-treated knees (P < 0.01). CONCLUSIONS: This is the first report of a potential therapy demonstrating a significant effect on bone shape measured by B-score in knee OA. These data, in combination with previously reported statistically significant and clinically meaningful improvements in WOMAC physical function versus placebo, support TPX-100 as a candidate for disease modification in knee OA. TRIAL REGISTRATION: NIH ClinicalTrials.gov, NCT01925261 . Registered 15 August 2013.

Machine-learning, MRI bone shape and important clinical outcomes in osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVES: Osteoarthritis (OA) structural status is imperfectly classified using radiographic assessment. Statistical shape modelling (SSM), a form of machine-learning, provides precise quantification of a characteristic 3D OA bone shape. We aimed to determine the benefits of this novel measure of OA status for assessing risks of clinically important outcomes. METHODS: The study used 4796 individuals from the Osteoarthritis Initiative cohort. SSM-derived femur bone shape (B-score) was measured from all 9433 baseline knee MRIs. We examined the relationship between B-score, radiographic Kellgren-Lawrence grade (KLG) and current and future pain and function as well as total knee replacement (TKR) up to 8 years. RESULTS: B-score repeatability supported 40 discrete grades. KLG and B-score were both associated with risk of current and future pain, functional limitation and TKR; logistic regression curves were similar. However, each KLG included a wide range of B-scores. For example, for KLG3, risk of pain was 34.4 (95% CI 31.7 to 37.0)%, but B-scores within KLG3 knees ranged from 0 to 6; for B-score 0, risk was 17.0 (16.1 to 17.9)% while for B-score 6, it was 52.1 (48.8 to 55.4)%. For TKR, KLG3 risk was 15.3 (13.3 to 17.3)%; while B-score 0 had negligible risk, B-score 6 risk was 35.6 (31.8 to 39.6)%. Age, sex and body mass index had negligible effects on association between B-score and symptoms. CONCLUSIONS: B-score provides reader-independent quantification using a single time-point, providing unambiguous OA status with defined clinical risks across the whole range of disease including pre-radiographic OA. B-score heralds a step-change in OA stratification for interventions and improved personalised assessment, analogous to the T-score in osteoporosis.

Disease-Modifying Effects of a Novel Cathepsin K Inhibitor in Osteoarthritis: A Randomized Controlled Trial.

Background: MIV-711 is a novel selective cathepsin K inhibitor with beneficial effects on bone and cartilage in preclinical osteoarthritis models. Objective: To evaluate the efficacy, safety, and tolerability of MIV-711 in participants with symptomatic, radiographic knee osteoarthritis. Design: 26-week randomized, double-blind, placebo-controlled phase 2a study with a 26-week open-label safety extension substudy. (EudraCT: 2015-003230-26 and 2016-001096-73). Setting: Six European sites. Participants: 244 participants with primary knee osteoarthritis, Kellgren-Lawrence grade 2 or 3, and pain score of 4 to 10 on a numerical rating scale (NRS). Intervention: MIV-711, 100 (n = 82) or 200 (n = 81) mg daily, or matched placebo (n = 77). Participants (46 who initially received 200 mg/d and 4 who received placebo) received 200 mg of MIV-711 daily during the extension substudy. Measurements: The primary outcome was change in NRS pain score. The key secondary outcome was change in bone area on magnetic resonance imaging (MRI). Other secondary end points included cartilage thickness on quantitative MRI and type I and II collagen C-telopeptide biomarkers. Outcomes were assessed over 26 weeks. Results: Changes in NRS pain scores with MIV-711 were not statistically significant (placebo, -1.4; MIV-711, 100 mg/d, -1.7; MIV-711, 200 mg/d, -1.5). MIV-711 significantly reduced medial femoral bone area progression (P = 0.002 for 100 mg/d and 0.004 for 200 mg/d) and medial femoral cartilage thinning (P = 0.023 for 100 mg/d and 0.125 for 200 mg/d) versus placebo and substantially reduced bone and cartilage biomarker levels. Nine serious adverse events occurred in 6 participants (1 in the placebo group, 3 in the 100 mg group, and 2 in the 200 mg group); none were considered to be treatment-related. Limitation: The trial was relatively short. Conclusion: MIV-711 was not more effective than placebo for pain, but it significantly reduced bone and cartilage progression with a reassuring safety profile. This treatment may merit further evaluation as a disease-modifying osteoarthritis drug. Primary Funding Source: Medivir.

Precision, Reliability, and Responsiveness of a Novel Automated Quantification Tool for Cartilage Thickness: Data from the Osteoarthritis Initiative.

OBJECTIVE: Accurate automated segmentation of cartilage should provide rapid reliable outcomes for both epidemiological studies and clinical trials. We aimed to assess the precision and responsiveness of cartilage thickness measured with careful manual segmentation or a novel automated technique. METHODS: Agreement of automated segmentation was assessed against 2 manual segmentation datasets: 379 magnetic resonance images manually segmented in-house (training set), and 582 from the Osteoarthritis Initiative with data available at 0, 1, and 2 years (biomarkers set). Agreement of mean thickness was assessed using Bland-Altman plots, and change with pairwise Student t test in the central medial femur (cMF) and tibia regions (cMT). Repeatability was assessed on a set of 19 knees imaged twice on the same day. Responsiveness was assessed using standardized response means (SRM). RESULTS: Agreement of manual versus automated methods was excellent with no meaningful systematic bias (training set: cMF bias 0.1 mm, 95% CI ± 0.35; biomarkers set: bias 0.1 mm ± 0.4). The smallest detectable difference for cMF was 0.13 mm (coefficient of variation 3.1%), and for cMT 0.16 mm(2.65%). Reported change using manual segmentations in the cMF region at 1 year was -0.031 mm (95% CI -0.022, -0.039), p < 10-4, SRM -0.31 (-0.23, -0.38); and at 2 years was -0.071 (-0.058, -0.085), p < 10-4, SRM -0.43 (-0.36, -0.49). Reported change using automated segmentations in the cMF at 1 year was -0.059 (-0.047, -0.071), p < 10-4, SRM -0.41 (-0.34, -0.48); and at 2 years was -0.14 (-0.123, -0.157, p < 10-4, SRM -0.67 (-0.6, -0.72). CONCLUSION: A novel cartilage segmentation method provides highly accurate and repeatable measures with cartilage thickness measurements comparable to those of careful manual segmentation, but with improved responsiveness.

Urine Specific Gravity as a Practical Marker for Identifying Suboptimal Fluid Intake of Runners ∼12-hr Postexercise.

The legitimacy of urine specific gravity (USG) as a stand-alone measure to detect hydration status has recently been challenged. As an alternative to hydration status, the purpose of this study was to determine the diagnostic capability of using the traditional USG marker of >1.020 to detect insufficient recovery fluid consumption with consideration for moderate versus high sweat losses (2.00-2.99 or >3% body mass, respectively). Adequate recovery fluid intake was operationally defined as ≥100% beverage fluid intake plus food water from one or two meals and a snack. Runners (n = 59) provided 132 samples from five previous investigations in which USG was assessed 10-14 hr after 60-90 min runs in temperate-to-hot environments. Samples were collected after a meal (n = 58) and after waking (n = 74). When sweat losses exceeded 3% body mass (n = 60), the relationship between fluid replacement percentage and USG increased from r = -.55 to -.70. Correct diagnostic decision improved from 66.6 to 83.3%, and receiver operating characteristic area under the curve increased the diagnostic accuracy score from 0.76 to approaching excellent (0.86). Artifacts of significant prerun hyperhydration (eight of 15 samples has USG <1.005) may explain false positive diagnoses, while almost all (84%) cases of false positives were found when sweat losses were <3.0% of body mass. Evidence from this study suggests that euhydrated runners experiencing significant sweat losses who fail to reach adequate recovery fluid intake levels can be identified by USG irrespective of acute meal and fluid intake ∼12-hr postrun.

Evaluation of segmentation methods on head and neck CT: Auto-segmentation challenge 2015.

PURPOSE: Automated delineation of structures and organs is a key step in medical imaging. However, due to the large number and diversity of structures and the large variety of segmentation algorithms, a consensus is lacking as to which automated segmentation method works best for certain applications. Segmentation challenges are a good approach for unbiased evaluation and comparison of segmentation algorithms. METHODS: In this work, we describe and present the results of the Head and Neck Auto-Segmentation Challenge 2015, a satellite event at the Medical Image Computing and Computer Assisted Interventions (MICCAI) 2015 conference. Six teams participated in a challenge to segment nine structures in the head and neck region of CT images: brainstem, mandible, chiasm, bilateral optic nerves, bilateral parotid glands, and bilateral submandibular glands. RESULTS: This paper presents the quantitative results of this challenge using multiple established error metrics and a well-defined ranking system. The strengths and weaknesses of the different auto-segmentation approaches are analyzed and discussed. CONCLUSIONS: The Head and Neck Auto-Segmentation Challenge 2015 was a good opportunity to assess the current state-of-the-art in segmentation of organs at risk for radiotherapy treatment. Participating teams had the possibility to compare their approaches to other methods under unbiased and standardized circumstances. The results demonstrate a clear tendency toward more general purpose and fewer structure-specific segmentation algorithms.

Opportunistic Quantitative CT Bone Mineral Density Measurement at the Proximal Femur Using Routine Contrast-Enhanced Scans: Direct Comparison With DXA in 355 Adults.

For patients undergoing routine contrast-enhanced CT examinations, an opportunity exists for concurrent osteoporosis screening without additional radiation exposure or patient time using proximal femur CT X-ray absorptiometry (CTXA). We investigated the effect of i.v. contrast enhancement on femoral neck CTXA T-score measurement compared with DXA. This cohort included 355 adults (277 female; mean age, 59.7 ± 13.3 years; range, 21 to 90 years) who underwent standard contrast-enhanced CT assessment at 120 kVp over an 8-year interval, as well as DXA BMD assessment within 100 days of the CT study (mean 46 ± 30 days). Linear regression and a Bland-Altman plot were performed to compare DXA and CTXA results. CTXA diagnostic sensitivity and specificity was evaluated with DXA as the reference standard. There was good correlation between DXA and CTXA (r2 = 0.824 for both areal BMD and T-scores) and the SD of the distribution of residuals was 0.063 g/cm2 or 0.45 T-score units. There was no trend in differences between the two measurements and a small bias was noted with DXA T-score +0.18 units higher than CTXA. CTXA had a sensitivity for discriminating normal from low bone mineral density of 94.9% (95% CI, 90.6% to 97.4%). For opportunistic osteoporosis screening at routine post-contrast abdominopelvic CT scans, CTXA produces T-scores similar to DXA. Because femoral neck CTXA BMD measurement is now included in the WHO Fracture Risk Assessment Tool (FRAX) tool, this opportunistic method could help to increase osteoporosis screening because it can be applied regardless of the clinical indication for CT scanning. © 2016 American Society for Bone and Mineral Research.

Direct Comparison of Unenhanced and Contrast-Enhanced CT for Opportunistic Proximal Femur Bone Mineral Density Measurement: Implications for Osteoporosis Screening.

OBJECTIVE: For patients undergoing contrast-enhanced CT examinations that include the proximal femur, an opportunity exists for concurrent screening bone mineral density (BMD) measurement. We investigated the effect of IV contrast enhancement on CT-derived x-ray absorptiometry areal BMD measurement. MATERIALS AND METHODS: Our cohort included 410 adults (mean age, 65.3 ± 10.0 years; range, 49-95 years) who underwent split-bolus CT urography at 120 kVp. Areal femoral neck BMD in g/cm(2) was measured on both unenhanced and contrast-enhanced CT series with asynchronous phantom calibration. Constant offset and multiplicative factor corrections for the contrast-enhanced series were derived from the Bland-Altman plot linear regression slopes. RESULTS: Mean unenhanced and contrast-enhanced areal femoral neck BMD values were 0.681 ± 0.118 and 0.713 ± 0.123 g/cm(2), respectively. The SD of the distribution of residuals for the constant offset and multiplicative model corrections were 0.0232 and 0.0231, respectively. The constant offset correction associated with contrast enhancement was 0.032 ± 0.023 g/cm(2), which corresponds to 0.29 ± 0.21 T-score units using the CT-derived x-ray absorptiometry young normal areal femoral neck BMD reference SD of 0.111 g/cm(2). CONCLUSION: For the purposes of opportunistic osteoporosis screening, contrast-enhanced abdominopelvic CT studies are equivalent to unenhanced CT and can therefore be used for femoral neck BMD assessment. This measure could greatly enhance osteoporosis screening.

Negative Impact of Aromatase Inhibitors on Proximal Femoral Bone Mass and Geometry in Postmenopausal Women with Breast Cancer.

Aromatase inhibitors (AIs), the standard therapy for estrogen receptor- or progesterone receptor-positive breast cancer in postmenopausal women, lead to increased hip fractures in breast cancer patients. To investigate the mechanism of increased incidence of hip fractures in breast cancer patients treated with AIs, we evaluated bone mineral density (BMD) in the cortical and trabecular compartments and assessed femoral geometry using quantitative computed tomography (QCT) in breast cancer patients. In total, 249 early breast cancer patients who underwent QCT in their fifties (mean age 54.3 years) were retrospectively analyzed. Proximal femoral BMD and geometrical parameters were compared. In all regions of the proximal femur, cortical areal BMDs were lower in the AI group than in the non-AI group (p < 0.05). Cortical thickness of the femoral neck, trochanter, and total hip was significantly lower in the AI group compared with the non-AI group (p < 0.05). Analysis of the narrowest section of the femoral neck showed significantly thinner cortical bone and smaller cortical area in the AI group than in the non-AI group (p < 0.05), especially in the superoposterior quadrant. Bone strength parameters in the femoral neck, such as the section modulus and cross-sectional moment of inertia, were significantly lower in the AI group than in the non-AI group (p < 0.05). In conclusion, AI treatment in breast cancer patients is associated with deterioration of femoral cortical BMD and geometry, which could contribute in site-specific weakened bone strength and increased incidence of hip fractures.

Performance of statistical models of shape and appearance for semiautomatic segmentations of spinal vertebrae T4-L4 on digitized vertebral fracture assessment images.

BACKGROUND CONTEXT: Despite its clinical importance, accurate identification of vertebral fractures is problematic and time-consuming. There is a recognized need to improve the detection of vertebral fractures so that appropriate high-risk patients can be selected to initiate clinically beneficial therapeutic interventions. PURPOSE: To develop and evaluate semiautomatic algorithms for detailed annotation of vertebral bodies from T4 to L4 in digitized lateral spinal dual-energy X-ray absorptiometry (DXA) vertebral fracture assessment (VFA) images. STUDY DESIGN: Using lateral spinal DXA VFA images from subjects imaged at University Hospital fracture liaison service, image algorithms were developed for semiautomatic detailed annotation of vertebral bodies from T4 to L4. PATIENT SAMPLE: Two hundred one women aged 50 years or older with nonvertebral fractures. OUTCOME MEASURES: Algorithm accuracy and precision. METHODS: Statistical models of vertebral shape and appearance from T4 to L4 were constructed using VFA images from 130 subjects. The resulting models form a part of an algorithm for performing semiautomatic detailed annotation of vertebral bodies from T4 to L4. Algorithm accuracy and precision were evaluated on a test-set of 71 independent images. RESULTS: Overall accuracy was 0.72 mm (3.00% of vertebral height) and overall precision was 0.26 mm (1.11%) for point-to-line distance. Accuracy and precision were best on normal vertebrae (0.65 mm [2.67%] and 0.21 mm [0.90%], respectively) and mild fractures (0.78 mm [3.18%] and 0.32 mm [1.39%], respectively), but accuracy and precision errors were higher for moderate (1.07 mm [4.66%] and 0.48 mm [2.15%], respectively) and severe fractures (2.07 mm [9.65%] and 1.10 mm [5.09%], respectively). Accuracy and precision results for the algorithm were comparable with other reported results in the literature. CONCLUSIONS: This semiautomatic image analysis had high overall accuracy and precision on normal vertebrae and mild fractures, but performed less well in moderate and severe fractures. It is, therefore, a useful tool to identify normality of vertebral shape and to identify mild fractures.

Quantitative computed tomography and opportunistic bone density screening by dual use of computed tomography scans.

Central dual-energy X-ray absorptiometry (DXA) of the lumbar spine and proximal femur is the preferred method for bone mineral density (BMD) testing. Despite the fracture risk statistics, osteoporosis testing with DXA remains underused. However, BMD can also be assessed with quantitative computed tomography (QCT) that may be available when access to DXA is restricted. For patients undergoing a primary CT study of the abdomen or pelvis, a potential opportunity exists for concurrent BMD screening by QCT without the need for any additional imaging, radiation exposure, or patient time.

Comparison of femoral neck BMD evaluation obtained using Lunar DXA and QCT with asynchronous calibration from CT colonography.

For patients undergoing screening computed tomography colonography (CTC), an opportunity exists for bone mineral density (BMD) screening without additional radiation exposure using quantitative computed tomography (QCT). This study investigated the use of dual-energy X-ray absorptiometry (DXA)-equivalent QCT Computed Tomography X-Ray Absorptiometry (CTXA) analysis at the hip obtained using CTC examinations using a retrospective asynchronous calibration of patient scans. A cohort of 33 women, age 61.3 (10.6) yr (mean [standard deviation]), had routine CTC using various GE LightSpeed CT scanner models followed after 0-9 mo by a DXA hip BMD examination using a GE Lunar Prodigy machine. Areal bone mineral density (aBMD) and T-scores of the proximal femur were measured from either prone or supine CTC examinations using Mindways QCT Pro software following standard workflow except that the CT scanners were asynchronously calibrated by phantoms scanned retrospectively of the CTC examination without the subject present. CTXA and DXA aBMD were highly correlated (R2=0.907) with a linear relationship of DXA_BMD=1.297*CTXA_BMD+0.048. The standard error of estimate (SEE) on the linear fit was 0.053 g/cm2. CTXA and DXA T-scores showed a linear relationship of DXA_T-score=1.034*CTXA_T-score+0.3 and an SEE of 0.379 T-scores. CTXA and DXA aBMD and T-score measurements showed good correlation despite asynchronous scan acquisition and retrospective QCT calibration. The SEE of 0.053 g/cm2 is on par with the literature comparing Hologic and Lunar DXA devices. The observed relationship between CTXA and Lunar DXA aBMD matches predictions from published cross-calibrations relating CTXA to DXA aBMD measurement. Thus, opportunistic use of CTXA T-scores obtained at the time of CTC could enhance osteoporosis screening.

Hydration kinetics and 10-km outdoor running performance following 75% versus 150% between bout fluid replacement.

Current American College of Sports Medicine (ACSM) guidelines recommend replacing 150% of sweat losses between training bouts separated by ≤12 hours, but little evidence exists concerning the implications of this strategy for runners. Participants (n = 13) in this study replaced 75% (1637 ± 372 mL) or 150% (3099 ± 850 mL) of sweat losses following an outdoor evening run (∼75 minutes; Wet-bulb-globe temperature (WBGT) = ∼27°C) and consumed a standardised evening meal and breakfast before completing an outdoor (WBGT = ∼23°C) 10-km time-trial the following morning. Urine was collected between runs and urine specific gravity (USG) was assessed pre-run. Significant differences were found in pre-run body mass (75% = 69.6 ± 9.2; 150% = 70.1 ± 9.3 kg; P = 0.02) and USG (75% = 1.026 ± 0.005; 150% = 1.014 ± 0.007; P < 0.001). Heart rate during 10-km run (168 ± 14 versus 168 ± 12 beats min(-1)) and post-run intestinal temperature (39.08 ± 0.52 versus 39.00 ± 0.70 °C) did not differ for 75% and 150%, respectively, despite an ∼3% performance improvement (75% = 47.28 ± 6.64; 150% = 45.93 ± 6.04 minutes; P = 0.001) due to a faster pace in the second half of the run with 150% replacement. Session rate of perceived exertion (RPE) was lower (P = 0.02) during 150% (7.5 ± 1.3) versus 75% (8.4 ± 0.9). Reluctant drinkers potentially hinder training quality between evening and morning runs in the heat, but copious urine production and difficulty in consuming recommended fluid volumes suggest fluid replacement <150% may be more ideal.

CTXA hip--an extension of classical DXA measurements using quantitative CT.

Bone mineral density (BMD) estimates for the proximal femur using Dual Energy X-ray Absorptiometry (DXA) are currently considered the standard for making a diagnosis of osteoporosis in an individual patient using BMD alone. We have compared BMD results from a commercial Quantitative CT (QCT) BMD analysis system, "CTXA Hip", which provides clinical data for the proximal femur, to results from DXA. We have also used CTXA Hip to determine cortical and trabecular contributions to total BMD. Sixty-nine patients were scanned using 3D QCT and DXA. CTXA Hip BMD measurements for Total Hip and Femoral Neck were compared to DXA results. Twenty-two women were scanned at 0, 1, 2 years and CTXA Hip and DXA results analyzed for long-term reproducibility. Long-term reproducibility calculated as root-mean-square averages of SDs in vivo was 0.012 g/cm2 (CV = 1.8%) for CTXA Total Hip and 0.011 g/cm2 (CV = 2.0%) for CTXA Femoral Neck compared to 0.014 g/cm2 (CV = 2.0%) and 0.016 g/cm2 (CV = 2.7%), respectively, for DXA. The correlation of Total Hip BMD CTXA vs. DXA was R = 0.97 and for Femoral Neck was R = 0.95 (SEE 0.044 g/cm2 in both cases). Cortical bone comprised 62±5% (mean ± SD) of total hipbone mass in osteoporotic women. CTXA Hip provides substantially the same clinical information as conventional DXA and in addition provides estimates of BMD in separate cortical and trabecular bone compartments, which may be useful in evaluation of bone strength.

Subchondral bone trabecular integrity predicts and changes concurrently with radiographic and magnetic resonance imaging-determined knee osteoarthritis progression.

OBJECTIVE: To evaluate subchondral bone trabecular integrity (BTI) on radiographs as a predictor of knee osteoarthritis (OA) progression. METHODS: Longitudinal (baseline, 12-month, and 24-month) knee radiographs were available for 60 female subjects with knee OA. OA progression was defined by 12- and 24-month changes in radiographic medial compartment minimal joint space width (JSW) and medial joint space area (JSA), and by medial tibial and femoral cartilage volume on magnetic resonance imaging. BTI of the medial tibial plateau was analyzed by fractal signature analysis using commercially available software. Receiver operating characteristic (ROC) curves for BTI were used to predict a 5% change in OA progression parameters. RESULTS: Individual terms (linear and quadratic) of baseline BTI of vertical trabeculae predicted knee OA progression based on 12- and 24-month changes in JSA (P < 0.01 for 24 months), 24-month change in tibial (P < 0.05), but not femoral, cartilage volume, and 24-month change in JSW (P = 0.05). ROC curves using both terms of baseline BTI predicted a 5% change in the following OA progression parameters over 24 months with high accuracy, as reflected by the area under the curve measures: JSW 81%, JSA 85%, tibial cartilage volume 75%, and femoral cartilage volume 85%. Change in BTI was also significantly associated (P < 0.05) with concurrent change in JSA over 12 and 24 months and with change in tibial cartilage volume over 24 months. CONCLUSION: BTI predicts structural OA progression as determined by radiographic and MRI outcomes. BTI may therefore be worthy of study as an outcome measure for OA studies and clinical trials.

Trabecular morphometry by fractal signature analysis is a novel marker of osteoarthritis progression.

OBJECTIVE: To evaluate the effectiveness of using subchondral bone texture observed on a radiograph taken at baseline to predict progression of knee osteoarthritis (OA) over a 3-year period. METHODS: A total of 138 participants in the Prediction of Osteoarthritis Progression study were evaluated at baseline and after 3 years. Fractal signature analysis (FSA) of the medial subchondral tibial plateau was performed on fixed flexion radiographs of 248 nonreplaced knees, using a commercially available software tool. OA progression was defined as a change in joint space narrowing (JSN) or osteophyte formation of 1 grade according to a standardized knee atlas. Statistical analysis of fractal signatures was performed using a new model based on correlating the overall shape of a fractal dimension curve with radius. RESULTS: Fractal signature of the medial tibial plateau at baseline was predictive of medial knee JSN progression (area under the curve [AUC] 0.75, of a receiver operating characteristic curve) but was not predictive of osteophyte formation or progression of JSN in the lateral compartment. Traditional covariates (age, sex, body mass index, knee pain), general bone mineral content, and joint space width at baseline were no more effective than random variables for predicting OA progression (AUC 0.52-0.58). The predictive model with maximum effectiveness combined fractal signature at baseline, knee alignment, traditional covariates, and bone mineral content (AUC 0.79). CONCLUSION: We identified a prognostic marker of OA that is readily extracted from a plain radiograph using FSA. Although the method needs to be validated in a second cohort, our results indicate that the global shape approach to analyzing these data is a potentially efficient means of identifying individuals at risk of knee OA progression.