PubMed Health⌕ Search

Biomedical subjects

F Cicuttini

Publications and source records attributed to F Cicuttini.

At least 19 recordsLinked to original sources

MRI protocols for whole-organ assessment of the knee in osteoarthritis.

One of the critical challenges in developing structure-modifying therapies for arthritis, especially osteoarthritis (OA), is measuring changes in progression of joint destruction. Magnetic resonance imaging (MRI) offers considerable promise in this regard. Not only can MRI quantify articular cartilage volume and morphology with high precision and accuracy, but it can also examine several other important articular components, and thus offer a unique opportunity to evaluate the knee and other joints as whole organs. On December 5 and 6, 2002, OMERACT (Outcome Measures in Rheumatology Clinical Trials) and OARSI (Osteoarthritis Research Society International), with support from various pharmaceutical companies listed at the beginning of this supplement, held a Workshop for Consensus on Osteoarthritis Imaging in Bethesda, MD. The aim of the Workshop was to provide a state-of-the-art review of imaging outcome measures for OA of the knee to help guide scientists and pharmaceutical companies who want to use MRI in multi-site studies of OA. Applications of MRI were initially reviewed by a multidisciplinary, international panel of expert scientists and physicians from academia, the pharmaceutical industry and regulatory agencies. The findings of the panel were then presented to a wider group of participants for open discussion. The following report summarizes the results of these discussions with respect to MRI acquisition techniques for whole-organ assessment of the knee in OA. The discussion reviews the selection and qualification of imaging sites for clinical trials, designing imaging protocols for whole-organ assessment of OA, and key considerations in image quality (IQ) control and data management.

Bone Marrow↗

Proposal for a nomenclature for magnetic resonance imaging based measures of articular cartilage in osteoarthritis.

OBJECTIVE: Magnetic resonance imaging (MRI) of articular cartilage has evolved to be an important tool in research on cartilage (patho)physiology and osteoarthritis (OA). MRI provides a wealth of novel and quantitative information, but there exists no commonly accepted terminology for reporting these metrics. The objective of this initiative was to propose a nomenclature for definitions and names to be used in scientific communications and to give recommendations as to which minimal methodological information should be provided when reporting MRI-based measures of articular cartilage in OA. METHODS: An international group of experts with direct experience in MRI measurement of cartilage morphology or composition reviewed the existing literature. Through an iterative process that included a meeting with a larger group of scientists and clinicians (December 2nd, 2004, Chicago, IL, USA), they discussed, refined, and proposed a nomenclature for MRI-based measures of articular cartilage in OA. RESULTS: The group proposes a nomenclature that describes: (1) the anatomical location and (2) the structural feature being measured, each name consisting of a metric variable combined with a tissue label. In addition, the group recommends minimal methodological information that should be described. CONCLUSIONS: Utilization of this nomenclature should facilitate communication within the scientific community. Further, the uniform adoption of comprehensive nomenclature to describe quantitative MRI- features of articular cartilage should strengthen epidemiological, clinical, and pharmacological studies in OA.

Cartilage, Articular↗

Magnetic resonance imaging (MRI) of articular cartilage in knee osteoarthritis (OA): morphological assessment.

OBJECTIVE: Magnetic resonance imaging (MRI) is a three-dimensional imaging technique with unparalleled ability to evaluate articular cartilage. This report reviews the current status of morphological assessment of cartilage with quantitative MRI (qMRI), and its relevance for identifying disease status, and monitoring progression and treatment response in knee osteoarthritis (OA). METHOD: An international panel of experts in MRI of knee OA, with direct experience in the analysis of cartilage morphology with qMRI, reviewed the existing published and unpublished data on the subject, and debated the findings at the OMERACT-OARSI Workshop on Imaging technologies (December 2002, Bethesda, MA) with scientists and clinicians from academia, the pharmaceutical industry and the regulatory agencies. This report reviews (1) MRI pulse sequence considerations for morphological analysis of articular cartilage; (2) techniques for segmenting cartilage; (3) semi-quantitative scoring of cartilage status; and (4) technical validity (accuracy), precision (reproducibility) and sensitivity to change of quantitative measures of cartilage morphology. RESULTS: Semi-quantitative scores of cartilage status have been shown to display adequate reliability, specificity and sensitivity, and to detect lesion progression at reasonable observation periods (1-2 years). Quantitative assessment of cartilage morphology (qMRI), with fat-suppressed gradient echo sequences, and appropriate image analysis techniques, displays high accuracy and adequate precision (e.g., root-mean-square standard deviation medial tibia=61 microl) for cross-sectional and longitudinal studies in OA patients. Longitudinal studies suggest that changes of cartilage volume of the order of -4% to -6% occur per annum in OA in most knee compartments (e.g., -90 microl in medial tibia). Annual changes in cartilage volume exceed the precision errors and appear to be associated with clinical symptoms as well as with time to knee arthroplasty. CONCLUSIONS: MRI provides reliable and quantitative data on cartilage status throughout most compartments of the knee, with robust acquisition protocols for multi-center trials now being available. MRI of cartilage has tremendous potential for large scale epidemiological studies of OA progression, and for clinical trials of treatment response to structure modifying OA drugs.

Cartilage, Articular↗

Comparison of conventional standing knee radiographs and magnetic resonance imaging in assessing progression of tibiofemoral joint osteoarthritis.

OBJECTIVE: Although the current recommendation is to measure radiographic joint space width (JSW) to assess structural change in osteoarthritis (OA), there is increasing interest in direct measurement of cartilage volume from magnetic resonance imaging (MRI). We performed a longitudinal study to compare change in both JSW and articular cartilage volume in subjects with symptomatic knee OA. METHODS: JSW was measured in 28 subjects with knee OA (57% females, mean age 62.8+/-9.8 years) who had standing radiographs in full extension, where both radiographs had satisfactory alignment. Each subject had femoral, tibial and combined femoral and tibial cartilage volumes determined from T1-weighted fat saturated sagittal knee MRI. All subjects had a repeat of the knee radiograph and MRI 1.96+/-0.4 years later. RESULTS: At baseline there was a moderate, but statistically significant, correlation between JSW and femoral and tibial cartilage volumes in the medial tibiofemoral joint, which was strengthened by adjusting for medial tibial bone size (R=0.58-0.66, P=0.001). Although we observed a reduction in JSW and femoral and tibial cartilage volumes over the study period, there was no significant association between reduction in JSW and cartilage volume (R<0.13). There was a trend towards a significant association between change in medial tibiofemoral cartilage volume and joint replacement at 4 years (OR=9.0, P=0.07) but not change in medial tibiofemoral JSW (OR=1.1, P=0.92). CONCLUSIONS: Although there was a modest correlation between cartilage volume and JSW in the medial tibiofemoral compartment, there was no correlation between longitudinal change in these measures. Change in cartilage volume appears to be a better predictor of joint replacement. Further work in larger samples over a longer period of time will be needed to confirm these findings.

Arthroplasty, Replacement, Knee↗

The management of scaphoid fractures.

Appropriate management of scaphoid fractures is important because of the risk of long-term complications such as delayed or non-union, pain and disability. Up to 25% of scaphoid fractures are not visible on the initial radiographs. Consequently, all clinically suspected scaphoid fractures are treated as fractures with cast immobilisation until cause of the symptoms is clarified. The diagnosis often utilises a number of second line investigations that are generally performed 10-14 days after the injury. Bone scintigraphy is currently the most commonly used of these as it rarely misses a fracture. However, it does not visualise anatomical structure and therefore alternative diagnoses are difficult. Magnetic resonance imaging (MRI) is at least as sensitive and more specific than bone scanning and has the advantages of being able to identify other lesions and not expose the patient to any radiation. Furthermore, the scan may be performed as early as 2.8 days following an injury rather than 10 days later in the case of a bone scan. Although the cost of MRI is higher than other imaging modalities, it may be cost-effective in the overall management of patients with occult scaphoid fractures since it may prevent unnecessary cast immobilisation in active people. The most appropriate method of cast immobilisation is presently unclear but evidence exists for improved clinical outcomes in those that have both the thumb and elbow immobilised for the first six weeks.

Diagnostic Imaging↗

Self-reported arthritis and the menopause.

OBJECTIVES: To determine the prevalence of self-reported arthritis in a population-based cohort of mid-aged women and to identify health, social and lifestyle factors associated with self-reported arthritis. DESIGN: Cross-sectional population-based survey. METHOD: Data were obtained from a telephone-administered questionnaire of 2001 Australian-born women between 45 and 55 years old and residing in Melbourne. Information was collected on demographics, lifestyle factors and health conditions. RESULTS: The most commonly reported symptom in this cohort was aches and stiff joints, reported by 51.7% of the women; 34.4% of participants reported they had been diagnosed with arthritis. More postmenopausal women (39%) reported that they were diagnosed with arthritis compared to premenopausal women (27%, p < 0.001). Women who reported arthritis were more likely to be older (odds radio (OR), 1.09; 95% confidence interval (CI), 1.05-1.13), have a higher body mass index (OR, 1.04; CI, 1.02-1.07), be postmenopausal (OR, 1.88; CI, 1.33-2.66), have a higher negative mood (OR, 1.80; CI, 1.13-2.87), and report a decreased interest in sex (OR, 1.58; CI, 1.26-1.97). CONCLUSIONS: Aches and stiff joints are the most frequently reported symptom of mid-aged women. Reported arthritis is associated with postmenopausal status, age, body mass index, less interest in sex and lowered mood. Further longitudinal research is needed to determine the role of these factors in the development and impact of arthritis.

Arthritis↗

Association between age and knee structural change: a cross sectional MRI based study.

OBJECTIVE: To describe the associations between age, knee cartilage morphology, and bone size in adults. METHODS: A cross sectional convenience sample of 372 male and female subjects (mean age 45 years, range 26-61) was studied. Knee measures included a cartilage defect five site score (0-4 respectively) and prevalence (defect score of > or =2 at any site), cartilage volume and thickness, and bone surface area and/or volume. These were determined at the patellar, medial, and lateral tibial and femoral sites using T(1)weighted fat saturation MRI. Height, weight, and radiographic osteoarthritis (ROA) were measured by standard protocols. RESULTS: In multivariate analysis, age was significantly associated with knee cartilage defect scores (beta = +0.016 to +0.073/year, all p<0.01) and prevalence (OR = 1.05-1.10/year, all p<0.05) in all compartments. Additionally, age was negatively associated with knee cartilage thickness at all sites (beta = -0.013 to -0.035 mm/year, all p<0.05), and with patellar (beta = -11.5 microl/year, p<0.01) but not tibial cartilage volume. Lastly, age was significantly positively associated with medial and lateral tibial surface bone area (beta = +3.0 to +4.7 mm(2)/year, all p<0.05) and patellar bone volume (beta = +34.4 microl/year, p<0.05). Associations between age and tibiofemoral cartilage defect score, cartilage thickness, and bone size decreased in magnitude after adjustment for ROA, suggesting these changes are directly relevant to OA. CONCLUSION: The most consistent knee structural changes with increasing age are increase in cartilage defect severity and prevalence, cartilage thinning, and increase in bone size with inconsistent change in cartilage volume. Longitudinal studies are needed to determine which of these changes are primary and confirm their relevance to knee OA.

Adult↗

Association between knee cartilage volume and bone mineral density in older adults without osteoarthritis.

OBJECTIVES: Studies have suggested an inverse association between osteoarthritis (OA) and osteoporosis, based on the presence of osteophytes rather than joint space narrowing (JSN), an indirect measure of joint cartilage. We conducted a cross-sectional study to determine the relationship between knee cartilage volume, a direct measure of joint cartilage, and bone mineral density (BMD) in an adult population. METHODS: 86 adults aged 55.1+/-10.4 years (50% females) had total BMD and bone mineral content (BMC) measured using dual X-ray absorptiometry. Site-specific BMD was performed on men in the study. Tibial and patella cartilage volumes were determined by processing images acquired in the sagittal plane using T(1)-weighted fat saturation magnetic resonance on an independent work station. RESULTS: Tibial knee cartilage volume was positively associated with total body BMD in both men and women after adjusting for age, BMI, tibial bone area and physical activity. In men, tibial cartilage volume was positively associated with proximal femur BMD, but not lumbar spine BMD. No relationship was seen between patellar cartilage volume and BMD at any region. CONCLUSIONS: We have shown a positive association between tibial cartilage volume and total BMD in men and women, but no such association with patellar cartilage volume. The mechanism for this is unclear but may represent a common environmental or genetic component. This study also highlights the need to examine the osteophyte and joint cartilage separately when investigating factors affecting the joint in health and disease since each feature is likely to reflect different aspects of the pathogenic process in OA.

Adult↗

Longitudinal study of the relationship between knee angle and tibiofemoral cartilage volume in subjects with knee osteoarthritis.

OBJECTIVES: There is emerging evidence that knee alignment is associated with progression of osteoarthritis (OA). The aim of this study was to examine the relationship between baseline knee angle and the rate of cartilage loss in subjects with knee OA. METHODS: One hundred and seventeen subjects with knee OA had standing radiographs and MRI on their symptomatic knee at baseline and at the 1.9+/-0.2 yr follow-up. Knee cartilage volume was measured at baseline and follow-up. Knee angle was defined as the angle subtended by a line drawn through the mid-shaft of the femur with respect to one drawn through the mid-shaft of the tibia. RESULTS: At baseline, in the medial compartment, as the angle decreased (i.e. was less varus) the tibial and femoral cartilage volume increased. In the lateral compartment, as the angle became more valgus, there was a reduction in tibial and femoral cartilage volume. In the longitudinal study, for every 1 degrees increase in baseline varus angulation there was an average annual loss of medial femoral cartilage of 17.7 micro l [95% confidence interval (CI) 6.5-28.8]. Although not statistically significant, there was a trend for a similar relationship between loss of medial tibial cartilage volume and baseline knee angle. In the lateral compartment, there was an average loss of tibial cartilage volume of 8.0 micro l (95% CI 0.0-16.0) for every 1 degrees increase in valgus angle. CONCLUSIONS: Baseline knee angle is associated with the rate of cartilage loss in the knee. Further work will be needed to determine whether therapies aimed at modifying the knee angle will reduce the progression of knee OA.

Aged↗

Early radiographic osteoarthritis is associated with substantial changes in cartilage volume and tibial bone surface area in both males and females.

OBJECTIVE: To describe the association between early radiographic osteoarthritis of the knee (ROA), knee cartilage volume and tibial bone surface area. METHODS: Cross-sectional convenience sample of 372 male and female subjects (mean age 45 years, range 26-61). Articular cartilage volume, bone area and volume were determined at the patella, medial tibial and lateral tibial compartments by processing images acquired in the sagittal plane using T1-weighted fat saturation MRI. ROA was assessed with a standing semiflexed radiograph and the OARSI atlas for joint space narrowing and osteophytosis. Both radiographs and MRIs were performed in the right knee and read by different observers. RESULTS: ROA (predominantly grade 1) was present in 17% of subjects of which medial joint space narrowing was most common (14%) followed by medial osteophytes (6%). Grade one medial joint space narrowing was associated with substantial reductions in cartilage volume at both the medial and lateral tibial and patellar sites within the knee (adjusted mean difference 11-13%, all P<0.001) while grade one osteophytosis was associated with substantial increases in both lateral and medial tibial joint surface area (adjusted mean difference 10-16%, all P<0.001). In contrast, osteophytosis was not associated with a significant change in cartilage volume and joint space narrowing was not associated with a significant change in tibial bone area (all P>0.05). CONCLUSIONS: Early medial compartment ROA is associated with substantial reductions in cartilage volume and increases in bone area. These large changes, when combined with similar measurement error for MRI and radiographs, suggest that MRI may be superior at detecting and hence understanding early osteoarthritis of the knee in humans.

Adult↗

Genetic mechanisms of knee osteoarthritis: a population based case-control study.

OBJECTIVE: To compare subjects who had at least one parent with a total knee replacement for severe primary knee osteoarthritis with age and sex matched controls who had no family history of knee osteoarthritis DESIGN: Population based case-control study of 188 matched pairs (mean age 45 years, range 26 to 60). METHODS: Articular cartilage volume and bone size were determined at the patella and at the medial tibial and lateral tibial compartments by processing images acquired using T1 weighted, fat saturated magnetic resonance imaging. Radiographic osteoarthritis (ROA) was assessed from a standing semiflexed radiograph scored for joint space narrowing and osteophytosis. Knee pain was assessed by questionnaire. Height, weight, body mass index (BMI), lower limb muscle strength, and endurance fitness were measured by standard protocols. RESULTS: Compared with the controls, index offspring had higher BMI (27.8 v 26.0 kg/m(2), p = 0.02), weaker lower limb muscles (127 v 135 kg, p = 0.006), more knee pain (47% v 22%, p<0.001), and greater medial tibial bone area (17.6 v 17.1 cm(2), p = 0.01). With the exception of BMI, these differences persisted in multivariate analysis. There was a non-significant trend to higher cartilage volume at tibial sites and increased ROA in the offspring in the total and subgroup analyses, but no difference in height and endurance fitness. CONCLUSIONS: BMI, muscle strength, knee pain, and medial tibial bone area, but not cartilage volume, appear to play a role in the genetic regulation and development of knee osteoarthritis.

Adult↗

Sex differences in knee cartilage volume in adults: role of body and bone size, age and physical activity.

OBJECTIVE: To test the hypothesis that sex differences in knee cartilage volume may be mediated through body and bone size, age and/or physical activity. METHODS: A cross-sectional convenience sample of 372 subjects (males 43%; mean age 45 yr, range 26-61) was studied. Articular cartilage volumes and bone size were determined at the patella, medial and lateral tibia by processing images acquired in the sagittal plane using T1-weighted fat saturation magnetic resonance imaging. Height, weight, physical activity (lower limb muscle strength, endurance fitness and questionnaire items) and radiographic osteoarthritis (ROA) were measured. RESULTS: Gender explained 33-42% of the variation in knee cartilage volumes (all P < 0.001). Males had 33-42% higher cartilage volume than females at all sites. In the whole group, the magnitude of sex differences decreased to 8-18% after adjustment for body height, weight and bone size, but remained significant (all P < 0.05). Further adjustment for physical activity had no effect on the sex differences. The sex differences in cartilage volume were greater in those aged over 50 compared with those aged under 50 (P < 0.05 for age-sex interaction at all sites) and were independent of ROA. CONCLUSIONS: Men have substantially higher knee cartilage volumes than women. These sex differences appear to be mediated in part by body and bone size but a significant amount remains unexplained. Furthermore, the differences become more marked over the age of 50 yr suggesting that both cartilage development and cartilage loss in later life contribute to sex differences in cartilage volume. Further longitudinal studies in large samples will be required to confirm these findings.

Adult↗

Trends and geographic variations in hospital admissions for asthma in Victoria. Opportunities for targeted interventions.

OBJECTIVE: To describe variations in rates of hospital admissions for asthma in Victoria as health indicators of quality of primary care services and access. DESIGN: Routine analyses of age and sex standardised admission rates of asthma in rural and metropolitan Victoria from 1993-1994 to 1999-2000. RESULTS: There were 10,079 admissions for asthma, with an average of 2.71 bed days in 1999-2000. The admission rate for asthma decreased from 3.1/1000 (95% CI: 3.1-3.2) in 1993-1994 to 2.2/1000 (2.1-2.2) in 1999-2000, with a 37% reduction in rural regions and 26% in metropolitan regions. Sixteen primary care partnerships (small areas), 13 of them rural, had significantly higher admission rates than the Victorian average. CONCLUSION: Although asthma hospital admission rates are falling faster in rural than metropolitan areas, rural areas still have higher admission rates with significant variation between small areas.

Age Distribution↗

Characterization of a human synovial cell antigen: VCAM-1 and inflammatory arthritis.

The contribution of synovial cells to the pathogenesis of rheumatoid arthritis (RA) is only partly understood. Monoclonal antibody (mAb) 1D5 is one of very few mAb ever raised against RA synovial cells in order to study the biology of these cells. Studies on the expression pattern and structural features of the 1D5 Ag suggest that 1D5 recognizes human vascular cell adhesion molecule-1 (VCAM-1), which is an intercellular adhesion molecule. Vascular cell adhesion molecule-1 may be involved in a number of crucial intercellular interactions in RA.

Animals↗

Vitamin E is ineffective for symptomatic relief of knee osteoarthritis: a six month double blind, randomised, placebo controlled study.

OBJECTIVE: There is a putative role for antioxidant treatment in osteoarthritis (OA) based on animal, epidemiological, and human clinical studies. Vitamin E, a fat soluble vitamin, is one of the major dietary antioxidants. Short term clinical studies using vitamin E in the form of alpha-tocopherol suggested a benefit over placebo of similar dimension to that of diclofenac for relief of OA pain. METHODS: A six month, double blind, randomised, placebo controlled study of vitamin E 500 IU/day was carried out. Primary outcome measures were pain, stiffness, and function. Statistical analysis was performed on an intention to treat basis. RESULTS: 77 patients were included in the study. Vitamin E showed no benefit over placebo at one month, three months, or six months for any of the outcome measures. The placebo group had higher pain levels (p=0.15) and body mass index (p=0.03) at baseline, and lower pain levels (p=0.02) at completion of the study. Radiological score, exercise score, age, or antioxidant intake at baseline or six months did not differ between the groups. The reasons for the better performance of the placebo group are uncertain but may relate to the initially higher pain score and subsequent regression to the mean. CONCLUSIONS: Vitamin E shows no benefit for the management of symptomatic knee OA. The role of vitamin E in preventing OA progression is currently under investigation.

Adult↗

Sex and site differences in cartilage development: a possible explanation for variations in knee osteoarthritis in later life.

OBJECTIVE: To test the hypothesis that sex-related and joint compartment-related differences in the risk of osteoarthritis (OA) of the knee might be associated with variations in cartilage development, we investigated knee cartilage volume in healthy children. METHODS: We studied 92 children who were randomly selected from among students in grades 3-12 of a single school in Hobart, Tasmania (49 boys, 43 girls; age range 9-18 years). Articular cartilage thickness and volume were determined at the patella, medial tibial compartment, and lateral tibial compartment by magnetic resonance imaging (MRI). Sagittal T1-weighted fat-suppressed MRI images were obtained and processed on an independent computer work station. RESULTS: Males had significantly more knee cartilage than females. Sex accounted for 6-36% of the variation in cartilage thickness and volume, which was statistically significant at all sites. Even after adjustment for age, body mass index, bone area, and physical activity, males had 16-31% higher cartilage volume; this was most marked at the medial tibial site. In addition, lateral tibial thickness was greater than medial tibial thickness (5.9 versus 3.6 mm; P < 0.0001) and lateral tibial volume was greater than medial tibial volume (2,823 versus 2,299 microl; P < 0.0001). Furthermore, physical activity was a significant explanatory factor for cartilage volume at all sites (R2 7-14% depending on site; all P < 0.05). The most consistent activity association was with vigorous activity in the previous 2 weeks (difference between any vigorous activity versus none 22-25% greater; all P < 0.05). CONCLUSION: Sex- and joint compartment-related differences in cartilage development may be one explanation for variations in the pattern of knee OA seen in later life. Furthermore, the physical activity associations suggest that cartilage development is amenable to modification.

Adolescent↗

Comparison and reproducibility of fast and conventional spoiled gradient-echo magnetic resonance sequences in the determination of knee cartilage volume.

Quantitation of articular cartilage by magnetic resonance imaging and three-dimensional reconstruction has been validated and is likely to be a useful outcome measure in clinical trials of arthritis. The cost of magnetic resonance imaging is largely dependent on scanning time. The aim of this study was to compare a fast spoiled gradient-echo sequence magnetic resonance imaging scanning protocol, which takes 5 minutes and 44 seconds, with the standard, previously validated spoiled gradient-echo sequence protocol, which takes 11 minutes and 56 seconds, in the measurement of knee cartilage volume. Cartilage volumes calculated from the standard and fast magnetic resonance imaging sequences were similar. The median absolute percentage overestimation or underestimation of the cartilage volume with the fast sequence for 10 normal subjects was 2.5, 4.1, and 3.2% for patellar, femoral, and tibial cartilage, respectively. For eight subjects with osteoarthritis, the percentages were 4.3 and 3.9% for femoral and tibial cartilage, respectively. The fast spoiled gradient-echo sequence protocol had very high intra-rater and inter-rater reproducibility in normal subjects and in those with osteoarthritis. Because the cost of magnetic resonance imaging scanning is largely determined by scan time, the faster scanning protocol means that the cost of estimates of knee cartilage volume can be significantly reduced, thus increasing the feasibility of this methodology.

Adult↗