Static Knee Alignment Measurements among Caucasians and African Americans: The Johnston County Osteoarthritis Project

Objective. To determine if knee alignment measures differ between African Americans and Caucasians without radiographic knee osteoarthritis (rOA). Methods. A single knee was randomly selected from 175 participants in the Johnston County Osteoarthritis Project without rOA in either knee. Anatomic axis, condylar, tibia] plateau, and condylar plateau angles were measured by I radiologist; means were compared and adjusted for age and body mass index (BMI). Results. There were no significant differences in knee alignment measurements between Caucasians and African Americans among men or women. Conclusion. Observed differences in knee rOA occurrence between African Americans and Caucasians are not explained by differences in static knee alignment. (First Release July 15 2009; J Rheumatol 2009;36:1987-90; doi: 10.3899/jrheum.081294)

Diagnosis and management of hyperprolactinemia: Results of a Brazilian multicenter study with 1234 patients

Objective: The aim of the study was to evaluate clinical and laboratorial features of 1234 patients with different etiologies of hyper-prolactinemia, as well as the response of 388 patients with prolactinomas to dopamine agonists. Design, setting, and patients: A total of 1234 hyperprolactinemic patients from 10 Brazilian endocrine centers were enrolled in this retrospective study. Main outcome measure: PRL measurement, thyroid function tests, and screening for macroprolactin were conducted. Results: Patients were subdivided as follows: 56.2% had prolactinomas, 14.5% drug-induced hyperprolactinemia, 9.3% macroprolactinemia, 6.6% non-functioning pituitary adenomas, 6.3% primary hypothyroidism, 3.6% idiopathic hyperprolactinemia, and 3.2% acromegaly. Clinical manifestations were similar irrespective of the etiology of the hyperprolactinemia. The highest PRL levels were observed in patients with prolactinomas but there was a great overlap in PRL values between all groups. However, PRL>500 ng/ml allowed a clear distinction between prolactinomas and the other etiologies. Cabergoline (CAB) was more effective than bromocriptine (BCR) in normalizing PRL levels (81.9% vs 67.1%, p<0.0001) and in inducing significant tumor shrinkage and complete disappearance of tumor mass. Drug resistance was observed in 10% of patients treated with CAB and in 18.4% of those that used BCR (p=0.0006). Side-effects and intolerance were also more common in BCR-treated patients. Conclusion: Prolactinomas, drug-induced hyperprolactinemia, and macroprolactinemia were the 3 most common causes of hyperprolactinemia. Although PRL levels could not reliably define the etiology of hyperprolactinemia, PRL values >500 ng/ml were exclusively seen in patients with prolactinomas. CAB was significantly more effective than BCR in terms of prolactin normalization, tumor shrinkage, and tolerability.

Effects of progressive resistance strength training on knee biomechanics during single leg step-up in persons with mild knee osteoarthritis

Background: The goal of this study was to determine if increasing strength in primary knee extensors and flexors would directly affect net knee joint moments during a common functional task in persons with knee osteoarthritis. Methods: An exploratory single sample clinical trial with pre-post treatment measures was used to study volunteers with clinical diagnosis of mild knee osteoarthritis (OA) in one knee. Subjects participated in an individually supervised training program 3 times a week for eight weeks consisting of progressive resistive exercises for knee extensors and knee flexors. Pre and post training outcome assessments included: 1. Net internal knee joint moments, 2. Electromyography of primary knee extensors and flexors, and 3. Self-report measures of knee pain and function. The distribution of lower extremity joint moments as a percent of the total support moment was also investigated. Findings: Pain, symptoms, activities of daily life, quality of life, stiffness, and function scores showed significant improvement following strength training. Knee internal valgus and hip internal rotation moments showed increasing but non-statistically significant changes post-training. There were no significant differences in muscle co-contraction activation of the Quadriceps and Hamstrings. Interpretation: While exercise continues to be an important element of OA management, the results of this study suggest improvements in function, pain, and other symptoms, as a result of strength training may not be causally related to specific biomechanical changes in net joint moments. (C) 2011 Elsevier Ltd. All rights reserved.

Long-Term Outcome and Prognostic Factors of Juvenile Dermatomyositis: A Multinational, Multicenter Study of 490 Patients

Objective. To investigate the long-term outcome and prognostic factors of juvenile dermatomyositis (DM) through a multinational, multicenter study. Methods. Patients consisted of inception cohorts seen between 1980 and 2004 in 27 centers in Europe and Latin America. Predictor variables were sex, continent, ethnicity, onset year, onset age, onset type, onset manifestations, course type, disease duration, and active disease duration. Outcomes were muscle strength/endurance, continued disease activity, cumulative damage, muscle damage, cutaneous damage, calcinosis, lipodystrophy, physical function, and health-related quality of life (HRQOL). Results. A total of 490 patients with a mean disease duration of 7.7 years were included. At the cross-sectional visit, 41.2-52.8% of patients, depending on the instrument used, had reduced muscle strength/endurance, but less than 10% had severe impairment. Persistently active disease was recorded in 41.2-60.5% of the patients, depending on the activity measure used. Sixty-nine percent of the patients had cumulative damage. The frequency of calcinosis and lipodystrophy was 23.6% and 9.7%, respectively. A total of 40.7% of the patients had decreased functional ability, but only 6.5% had major impairment. Only a small fraction had decreased HRQOL. A chronic course, either polycyclic or continuous, consistently predicted a poorer outcome. Mortality rate was 3.1%. Conclusion. This study confirms the marked improvement in functional outcome of juvenile DM when compared with earlier literature. However, many patients had continued disease activity and cumulative damage at followup. A chronic course was the strongest predictor of poor prognosis. These findings highlight the need for treatment strategies that enable a better control of disease activity over time and the reduction of nonreversible damage.

Advances in Imaging of Osteoarthritis and Cartilage

Osteoarthritis (OA) is the most frequent form of arthritis, with major implications for individual and public health care without effective treatment available. The field of joint imaging, and particularly magnetic resonance (MR) imaging, has evolved rapidly owing to technical advances and the application of these to the field of clinical research. Cartilage imaging certainly is at the forefront of these developments. In this review, the different aspects of OA imaging and cartilage assessment, with an emphasis on recent advances, will be presented. The current role of radiography, including advances in the technology for joint space width assessment, will be discussed. The development of various MR imaging techniques capable of facilitating assessment of cartilage morphology and the methods for evaluating the biochemical composition of cartilage will be presented. Advances in quantitative morphologic cartilage assessment and semiquantitative whole-organ assessment will be reviewed. Although MR imaging is the most important modality in imaging of OA and cartilage, others such as ultrasonography play a complementary role that will be discussed briefly.

Magnetic Resonance Imaging Assessment of Subchondral Bone and Soft Tissues in Knee Osteoarthritis

Knee osteoarthritis (OA) has to be considered a whole joint disease. Magnetic resonance imaging (MRI) allows superior assessment of all joint tissues that may be involved in OA, such as the subchondral bone, synovium, ligaments, and periarticular soft tissues. Reliable MRI-based scoring systems are available to assess and quantify these structures and associated pathology. Cross-sectional and longitudinal evaluation has enabled practitioners to understand their relevance in explaining pain and structural progression.

Magnetic Resonance Imaging in Knee Osteoarthritis Research: Semiquantitative and Compositional Assessment

Semiquantitative assessment of the knee by expert magnetic resonance imaging readers is a powerful research tool for understanding the natural history of osteoarthritis (OA). Several reliable semiquantitative scoring systems have been applied to large observational cross-sectional and longitudinal epidemiologic studies and interventional clinical trials. Such evaluations have enabled understanding of the relevance of disease in structures within the knee joint to explain pain and progression of OA. Compositional imaging of cartilage has added to our ability to detect early degeneration before morphologic changes are present, which may help to prevent the permanent morphologic changes commonly seen in knee OA.

Comparison of differentiated dendritic cell infiltration of autoimmune and osteoarthritis synovial tissue

Objective. Infiltration of rheumatoid arthritis (RA) synovial tissue (ST) by differentiated dendritic cells (DC) is a consistent feature in patients with active disease. However, mononuclear cells (MNC), including DC, may be nonspecifically chemoattracted to inflammatory sites regardless of etiology, Therefore, to evaluate the specificity of ST infiltration by differentiated DC, synovial biopsies from patients with RA, spondylarthropathy (SpA), osteoarthritis (OA), and gout were examined. Methods. Formalin-fixed ST sections were analyzed by double immunohistochemical staining for vascularity and infiltration by differentiated DC, lymphocytes, and macrophages. Results, DC containing nuclear RelB were found in perivascular MNC aggregates from patients with all arthritides studied. Infiltration by differentiated DC was similar in RA and SpA ST, but reduced in OA ST. Differentiated DC were always observed in close association with lymphocytes, and the correlation between these variables suggested that the infiltration of inflammatory sites by DC and lymphocytes was associated. Conclusion, Perivascular infiltration by DC, lymphocytes, and macrophages is nonspecifically related to inflammation, but signals present in RA and SpA ST lead to more intense cellular infiltration and accumulation.

Living with osteoarthritis: Patient expenditures, health status, and social impact

Objective. To determine out-of-pocket expenditures related to osteoarthritis (OA) and to explore whether demographic details, health status scores (Medical Outcomes Study 36-item Short Form [SF-36] and Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), or perception of social effect were expenditure determinants. Methods. A prospective cohort study of community-dwelling subjects with OA completed 4 consecutive 3-month cost diaries. In addition, subjects completed the SF-36 and WOMAC at baseline and at 12 months. Social impact at baseline was collected. Four groups categorized by age and sex were compared. Patients undergoing joint replacement were excluded. Results. Differences in health status were defined more by age than by sex, especially for physical function. The costs to the patients were high, particularly for women, who spent more on medications and special equipment. Women also reported receiving more assistance from family and friends. Higher disease-related expenditures were associated with greater pain levels, poorer social function and mental health, and longer duration of disease. Significant independent predictors of total patient expenditures related to OA were being female and having joint stiffness. Conclusion. Despite having heavily subsidized health care and access to the Pharmaceutical Benefits Scheme, out-of-pocket costs for patients with OA in Australia are considerable. Higher expenditures for patients with OA are related to more advanced disease, especially for women.

The ratio of messenger RNA levels of receptor activator of nuclear factor kappa B ligand to osteoprotegerin correlates with bone remodeling indices in normal human cancellous bone but not in osteoarthritis

skeletal disease. Bone remodeling is initiated by osteoclastic resorption followed by osteoblastic formation of new bone. Receptor activator of nuclear factor KB ligand (RANKL) is a newly described regulator of osteoclast formation and function, the activity of which appears to be a balance between interaction with its receptor RANK and with an antagonist binding protein osteoprotegerin (OPG). Therefore, we have examined the relationship between the expression of RANKL, RANK, and OPG and indices of bone structure and turnover in human cancellous bone from the proximal femur. Bone samples were obtained from individuals with osteoarthritis (OA) at joint replacement surgery and from autopsy controls. Histomorphometric analysis of these samples showed that eroded surface (ES/BS) and osteoid surface (OS/BS) were positively associated in both control (p < 0.001) and OA (p < 0.02), indicating that the processes of bone resorption and bone formation remain coupled in OA, as they are in controls. RANKL, OPG, and RANK messenger RNA, (mRNA) were abundant in human cancellous bone, with significant differences between control and OA individuals. In coplotting the molecular and histomorphometric data, strong associations were found between the ratio of RANKL/OPG mRNA and the indices of bone turnover (RANKL/OPG vs. ES/BS: r = 0.93, p < 0.001; RANKL/OPG vs. OS/BS: r = 0.80, p < 0.001). These relationships were not evident in trabecular bone from severe OA, suggesting that bone turnover may be regulated differently in this disease. We propose that the effective concentration of RANKL is related causally to bone turnover.

A cross-sectional study of the association between Heberden's nodes, radiographic osteoarthritis of the hands, grip strength, disability and pain

Objective: To describe the associations between hand osteoarthritis (OA), pain and disability in males and females and to further validate the Australian/Canadian CA hand index (AUSCAN LK3.0). Design: Cross-sectional study of 522 subjects from 101 Tasmanian families (males N=174, females N=348). Hand OA was assessed by two observers using the Altman atlas for joint space narrowing and osteophytes at distal interphalangeal and first carpometacarpal joints as well as a score for Heberden's nodes based on hand photography. Hand pain and function were assessed by the AUSCAN LK3.0 and grip strength by dynamometry in both hands on two occasions. Results: The prevalence of hand CA was high in this sample at 44-71% (depending on site). Pain and dysfunction increased with age while grip strength decreased (all P <0.001). All three measures were markedly worse in women, even after taking the severity of arthritis into account. Hand CA explained 5.7-10% of the variation in function, grip strength and pain scores, even after adjustment for age and sex. Further adjustment suggested that the osteoarthritic associations with function and grip strength were largely mediated by pain. Severity of disease was more strongly associated with these scores than presence or absence. Lastly, the AUSCAN LK3.0 showed a comparable association to grip strength with structural damage providing further evidence of index validity. Conclusions: Hand CA at these two sites makes substantial contributions to hand function, strength and pain. The associations with function and strength measures appear mediated by pain. Gender differences in all three measures persist after adjustment for variation in age and CA severity indicating that factors apart from radiographic disease are responsible. (C) 2001 OsteoArthritis Research Society International.

Towards a definition of "difference" in osteoarthritis

To assess existing information regarding detectable differences in osteoarthritis (OA), a systematic literature search was conducted up to December 1999. Thirty-three articles were considered methodologically relevant to the definition and categorization of detectable differences in OA. It was determined that the musculoskeletal literature contains a wealth of information that relates to observed changes, much of which is derived from the clinical trials literature, but there have been relatively few methodological studies that have systematically evaluated the nature, categorization, and relevance of the change. Furthermore, most of those that have been published take the perspective of an individual or groups of experts other than that of the patient. This summary of the current literature reveals that the diverse sources of information go part way towards developing an understanding of detectable differences and their importance in the area of OA research and clinical practice. Stakeholders' interests as well as factors that modulate perceptions of importance need to be taken under consideration. In particular, the patient's perspective of the importance of change at an individual level requires further evaluation. This area of clinical research is relatively underdeveloped, but there is considerable opportunity for progress.