Backbonding in Thorium(IV) and Uranium(IV) Diarsenido Complexes with tBuNC and CO.

The coordination of tBuNC and CO with the diarsenido complexes (C5 Me5 )2 An(η2 -As2 Mes2 ), An=Th, U, has been investigated. For the first time, a comparison between isostructural complexes of ThIV and UIV has been possible with CO; density functional calculations indicated an appreciable amount of π backbonding that originates from charge transfer from an actinide-arsenic sigma bond. The calculated CO stretching frequencies in the ThIV and UIV diarsenido complexes are consistent with the experimental measurements, both show large shifts to lower frequency. We demonstrate that the π backbonding is crucial to explaining the red shifts of CO frequency upon AnIV complex formation. Interestingly, this interaction essentially correlates to the parallel orientation of π*(C-O) orbitals relative to the An-As bond.

Risk factors and the natural history of accelerated knee osteoarthritis: a narrative review.

BACKGROUND: Osteoarthritis is generally a slowly progressive disorder. However, at least 1 in 7 people with incident knee osteoarthritis develop an abrupt progression to advanced-stage radiographic disease, many within 12 months. We summarize what is known - primarily based on findings from the Osteoarthritis Initiative - about the risk factors and natural history of accelerated knee osteoarthritis (AKOA) - defined as a transition from no radiographic knee osteoarthritis to advanced-stage disease < 4 years - and put these findings in context with typical osteoarthritis (slowly progressing disease), aging, prior case reports/series, and relevant animal models. Risk factors in the 2 to 4 years before radiographic manifestation of AKOA (onset) include older age, higher body mass index, altered joint alignment, contralateral osteoarthritis, greater pre-radiographic disease burden (structural, symptoms, and function), or low fasting glucose. One to 2 years before AKOA onset people often exhibit rapid articular cartilage loss, larger bone marrow lesions and effusion-synovitis, more meniscal pathology, slower chair-stand or walking pace, and increased global impact of arthritis than adults with typical knee osteoarthritis. Increased joint symptoms predispose a person to new joint trauma, which for someone who develops AKOA is often characterized by a destabilizing meniscal tear (e.g., radial or root tear). One in 7 people with AKOA onset subsequently receive a knee replacement during a 9-year period. The median time from any increase in radiographic severity to knee replacement is only 2.3 years. Despite some similarities, AKOA is different than other rapidly progressive arthropathies and collapsing these phenomena together or extracting results from one type of osteoarthritis to another should be avoided until further research comparing these types of osteoarthritis is conducted. Animal models that induce meniscal damage in the presence of other risk factors or create an incongruent distribution of loading on joints create an accelerated form of osteoarthritis compared to other models and may offer insights into AKOA. CONCLUSION: Accelerated knee osteoarthritis is unique from typical knee osteoarthritis. The incidence of AKOA in the Osteoarthritis Initiative and Chingford Study is substantial. AKOA needs to be taken into account and studied in epidemiologic studies and clinical trials.

Repeating Vertebral Fracture Assessment: 2019 ISCD Official Position.

Vertebral fracture (VF) is the most common type of osteoporotic fracture. VFs are associated with a decline in quality of life and high morbidity and mortality. The presence of a VF is a significant risk factor for developing another fracture; however, most VFs are not clinically recognized and diagnosed. Vertebral fracture assessment by dual-energy X-ray absorptiometry is a low cost, low radiation, convenient, and reliable method to identify VFs. The finding of a previously unrecognized VF may change the assessment of fracture risk, diagnostic classification, and treatment strategies. Vertebral fracture assessment or radiographic lateral spine imaging should be repeated in patients with continued high risk for fracture (e.g., historical height loss >4 cm [>1.5 inches], self-reported but undocumented vertebral fracture, or glucocorticoid therapy equivalent to ≥5 mg of prednisone or equivalent per day for greater than or equal to 3 months).

Accelerated Knee Osteoarthritis Is Characterized by Destabilizing Meniscal Tears and Preradiographic Structural Disease Burden.

OBJECTIVE: To determine whether accelerated knee osteoarthritis (KOA) is preceded by, and characterized over time by, destabilizing meniscal tears or other pathologic changes. METHODS: We selected 3 sex-matched groups of subjects from the first 48 months of the Osteoarthritis Initiative, comprising adults who had a knee without KOA (Kellgren/Lawrence [K/L] radiographic grade <2) at baseline. Subjects in the accelerated KOA group developed KOA of K/L grade ≥3, those with typical KOA showed increased K/L radiographic scores, and those with no KOA had the same K/L grade over time. An index visit was the visit when the radiographic criteria for accelerated KOA and typical KOA were met (the no KOA group was matched to the accelerated KOA group). The observation period was up to 2 years before and after an index visit. Radiologists reviewed magnetic resonance (MR) images of the index knee and identified destabilizing meniscal tears (root tears, radial tears, complex tears), miscellaneous pathologic features (acute ligamentous or tendinous injuries, attrition, subchondral insufficiency fractures, other incidental findings), and meniscal damage in >2 of 6 regions (3 regions per meniscus: anterior horn, body, posterior horn). In addition, bone marrow lesions (BMLs) and cartilage damage on MR images were quantified. Linear mixed regression models were performed to analyze the results. RESULTS: At 1 year before the index visit, >75% of adults with accelerated KOA had meniscal damage in ≥2 regions (odds ratio 3.19 [95% confidence interval 1.70-5.97] versus adults with typical KOA). By the index visit, meniscal damage in ≥2 regions was ubiquitous in adults with accelerated KOA, including 42% of subjects having evidence of a destabilizing meniscal tear (versus 14% of subjects with typical KOA). These changes corresponded to findings of larger BMLs and greater cartilage loss in the accelerated KOA group. CONCLUSION: Accelerated KOA is characterized by destabilizing meniscal tears in a knee compromised by meniscal damage in >2 regions, and also characterized by the presence of large BMLs and greater cartilage loss.

Opportunistic Screening for Osteoporosis Using Computed Tomography: State of the Art and Argument for Paradigm Shift.

PURPOSE OF REVIEW: Osteoporosis is disproportionately common in rheumatology patients. For the past three decades, the diagnosis of osteoporosis has benefited from well-established practice guidelines that emphasized the use of dual x-ray absorptiometry (DXA). Despite these guidelines and the wide availability of DXA, approximately two thirds of eligible patients do not undergo testing. One strategy to improve osteoporosis testing is to employ computed tomography (CT) examinations obtained as part of routine patient care to "opportunistically" screen for osteoporosis, without additional cost or radiation exposure to patients. This review examines the role of opportunistic CT in the evaluation of osteoporosis. RECENT FINDINGS: Recent evidence suggests that opportunistic measurement of bone attenuation (radiodensity) using CT has sensitivity comparable to DXA. More importantly, such an approach has been shown to predict osteoporotic fractures. The paradigm shift of using CTs obtained for other reasons to opportunistically screen for osteoporosis promises to substantially improve patient care.

ACR Appropriateness Criteria® Suspected Osteomyelitis, Septic Arthritis, or Soft Tissue Infection (Excluding Spine and Diabetic Foot).

Infection of the musculoskeletal system is a common clinical problem. Differentiating soft tissue from osseous infection often determines the appropriate clinical therapeutic course. Radiographs are the recommend initial imaging examination, and although often not diagnostic in acute osteomyelitis, can provide anatomic evaluation and alternative diagnoses influencing subsequent imaging selection and interpretation. MRI with contrast is the examination of choice for the evaluation of suspected osteomyelitis, and MRI, CT, and ultrasound can all be useful in the diagnosis of soft tissue infection. CT or a labeled leukocyte scan and sulfur colloid marrow scan combination are alternative options if MRI is contraindicated or extensive artifact from metal is present. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria Follow-Up of Malignant or Aggressive Musculoskeletal Tumors.

Appropriate imaging modalities for the follow-up of malignant or aggressive musculoskeletal tumors include radiography, MRI, CT, (18)F-2-fluoro-2-deoxy-D-glucose PET/CT, (99m)Tc bone scan, and ultrasound. Clinical scenarios reviewed include evaluation for metastatic disease to the lung in low- and high-risk patients, for osseous metastatic disease in asymptomatic and symptomatic patients, for local recurrence of osseous tumors with and without significant hardware present, and for local recurrence of soft tissue tumors. The timing for follow-up of pulmonary metastasis surveillance is also reviewed. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Evaluation of bone marrow lesion volume as a knee osteoarthritis biomarker--longitudinal relationships with pain and structural changes: data from the Osteoarthritis Initiative.

INTRODUCTION: Bone marrow lesion (BML) size may be an important imaging biomarker for osteoarthritis-related clinical trials and reducing BML size may be an important therapeutic goal. However, data on the interrelationships between BML size, pain, and structural progression are inconsistent and rarely examined in the same cohort. Therefore, we evaluated the cross-sectional and longitudinal associations of BML volume with knee pain and joint space narrowing (JSN). METHODS: A BML volume assessment was performed on magnetic resonance images of the knee collected at the 24- and 48-month Osteoarthritis Initiative visits from a convenience sample of 404 participants in the progression cohort. During the same visits, knee pain was assessed with WOMAC pain scores and knee radiographs were acquired and scored for JSN. BML volume was summed to generate a total knee volume and an index tibiofemoral compartment volume (compartment with greater baseline JSN). Primary analyses included multiple linear regressions (outcome = pain, predictor = total knee BML volume) and logistic regressions (outcome = JSN, predictor = index tibiofemoral compartment BML volume). RESULTS: This sample was 49% female with a mean age of 63 (9.2 standard deviation (SD)) years, and 71% had radiographic osteoarthritis in the study knee. Larger baseline BMLs were associated with greater baseline knee pain (P = 0.01), the presence of JSN at baseline (odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.23 to 1.83), and JSN progression (OR = 1.27, 95%CI = 1.11 to 1.46). Changes in total knee BML volume had a positive association with changes in knee pain severity (P = 0.004) and this association may be driven by knees that were progressing from no or small baseline BMLs to larger BMLs. In contrast, we found no linear positive relationship between BML volume change and JSN progression. Instead, regression of medial tibiofemoral BML volume was associated with JSN progression compared to knees with no or minimal changes in BML volume (OR = 3.36, 95%CI = 1.55 to 7.28). However, follow-up analyses indicated that the association between JSN progression and BML volume change may primarily be influenced by baseline BML volume. CONCLUSION: Large baseline BMLs are associated with greater baseline knee pain, the presence of JSN at baseline, and disease progression. Additionally, BML regression is associated with decreased knee pain but not a reduced risk of concurrent JSN progression.

Quantification of bone marrow lesion volume and volume change using semi-automated segmentation: data from the osteoarthritis initiative.

BACKGROUND: To determine the validity of a semi-automated segmentation of bone marrow lesions (BMLs) in the knee. METHODS: Construct validity of the semi-automated BML segmentation method was explored in two studies performed using sagittal intermediate weighted, turbo spine echo, fat-suppressed magnetic resonance imaging sequences obtained from the Osteoarthritis Initiative. The first study (n = 48) evaluated whether tibia BML volume was different across Boston Leeds Osteoarthritis Knee Scores (BLOKS) for tibia BMLs (semiquantitative grades 0 to 3). In the second study (n = 40), we evaluated whether BML volume change was associated with changes in cartilage parameters. The knees in both studies were segmented by one investigator. We performed Wilcoxon signed-rank tests to determine if tibia BML volume was different between adjacent BLOKS BML scores and calculated Spearman correlation coefficients to assess the relationship between 2-year BML volume change and 2-year cartilage morphometry change (significance was p ≤ 0.05). RESULTS: BML volume was significantly greater between BLOKS BML score 0 and 1 (z = 2.85, p = 0.004) and BLOKS BML scores 1 and 2 (z = 3.09, p = 0.002). There was no significant difference between BLOKS BML scores 2 and 3 (z = -0.30, p = 0.77). Increased tibia BML volume was significantly related to increased tibia denuded area (Spearman r = 0.42, p = 0.008), decreased tibia cartilage thickness (Spearman r = -0.46, p = 0.004), increased femur denuded area (Spearman r = 0.35, p = 0.03), and possibly decreased femur cartilage thickness (Spearman r = -0.30, p = 0.07) but this last finding was not statistically significant. CONCLUSION: The new, efficient, and reliable semi-automated BML segmentation method provides valid BML volume measurements that increase with greater BLOKS BML scores and confirms previous reports that BML size is associated with longitudinal cartilage loss.

Bone marrow lesion volume reduction is not associated with improvement of other periarticular bone measures: data from the Osteoarthritis Initiative.

INTRODUCTION: We evaluated the associations between bone marrow lesion (BML) volume change and changes in periarticular bone mineral density (paBMD) as well as subchondral sclerosis to determine whether BML change is associated with other local bone changes. METHODS: The convenience sample comprised participants in the Osteoarthritis Initiative (OAI) with weight-bearing posterior-anterior knee radiographs and magnetic resonance images (MRIs) at the 24- and 48-month visits and dual-energy x-ray absorptiometry (DXA) at the 30-/36-month and 48-month visits. The right knee was assessed unless contraindicated for MRI. We used knee DXA scans to measure medial tibia paBMD and medial/lateral paBMD ratio (M:L paBMD). Knee radiographs were scored for sclerosis (grades 0 to 3) in the medial tibia. Two raters determined BML volume on sagittal fat-suppressed MRI by using a semiautomated segmentation method. To focus on knees with only medial tibia BML changes, knees with lateral tibial BMLs were excluded. Medial tibial BML volume change was classified into three groups: BML regression (lowest quartile of medial tibial BML volume change), no-to-minimal change (middle two quartiles), and BML progression (highest quartile). We used proportional odds logistic regression models to evaluate the association between quartiles of changes in medial paBMD or M:L paBMD ratio, as outcomes, and BML volume change. RESULTS: The sample (n = 308) included 163 (53%) female subjects, 212 (69%) knees with radiographic osteoarthritis, and participants with a mean age of 63.8 ± 9.3 years and mean body mass index of 29.8 ± 4.7 kg/m(2). We found an association between greater increases in medial tibia paBMD and BML regression (OR = 1.7 (95% confidence interval (CI) = 1.1 to 2.8)) and a similar trend for BML progression (OR = 1.6 (95% CI = 1.0 to 2.6]). We also detected associations between greater increase in M:L paBMD and BML regression (OR = 1.6 (95% CI = 1.0 to 2.7]) and BML progression (OR = 1.8 (95% CI = 1.1 to 3.0)), although BML regression had borderline statistical significance. The frequency of sclerosis progression in the medial tibia (n = 14) was greater among knees with BML progression or regression compared with knees without BML change (P = 0.01 and P = 0.04, respectively). CONCLUSION: BML regression and BML progression are characterized by concurrent increases in paBMD and sclerosis, which are characteristic of increased radiographic osteoarthritis severity. At least during 24 months, BML regression is not representative of improvement in other periarticular bone measures.

Quantitative bone marrow lesion size in osteoarthritic knees correlates with cartilage damage and predicts longitudinal cartilage loss.

BACKGROUND: Bone marrow lesions (BMLs), common osteoarthritis-related magnetic resonance imaging findings, are associated with osteoarthritis progression and pain. However, there are no articles describing the use of 3-dimensional quantitative assessments to explore the longitudinal relationship between BMLs and hyaline cartilage loss. The purpose of this study was to assess the cross-sectional and longitudinal descriptive characteristics of BMLs with a simple measurement of approximate BML volume, and describe the cross-sectional and longitudinal relationships between BML size and the extent of hyaline cartilage damage. METHODS: 107 participants with baseline and 24-month follow-up magnetic resonance images from a clinical trial were included with symptomatic knee osteoarthritis. An 'index' compartment was identified for each knee defined as the tibiofemoral compartment with greater disease severity. Subsequently, each knee was evaluated in four regions: index femur, index tibia, non-index femur, and non-index tibia. Approximate BML volume, the product of three linear measurements, was calculated for each BML within a region. Cartilage parameters in the index tibia and femur were measured based on manual segmentation. RESULTS: BML volume changes by region were: index femur (median [95% confidence interval of the median]) 0.1 cm3 (-0.5 to 0.9 cm3), index tibia 0.5 cm3 (-0.3 to 1.7 cm3), non-index femur 0.4 cm3 (-0.2 to 1.6 cm3), and non-index tibia 0.2 cm3 (-0.1 to 1.2 cm3). Among 44 knees with full thickness cartilage loss, baseline tibia BML volume correlated with baseline tibia full thickness cartilage lesion area (r = 0.63, p< 0.002) and baseline femur BML volume with longitudinal change in femoral full thickness cartilage lesion area (r = 0.48 p< 0.002). CONCLUSIONS: Many regions had no or small longitudinal changes in approximate BML volume but some knees experienced large changes. Baseline BML size was associated to longitudinal changes in area of full thickness cartilage loss.