Osteoarthritis is a chronic disease for which no efficacious medical intervention is yet available. Recent disappointments in late-stage clinical development of disease-modifying osteoarthritic drugs (DMOADs) have precipitated efforts in biomarker discovery aimed at developing an analytical tool box with the potential to improve the clinical development process. In this review, we seek to provide an overview of the biochemical marker repertoire currently available with a special focus on data originating from their application in clinical development programmes. Finally, we discuss possible directions in future biomarker research.
Our aims were to translate WOMAC and Lequesne osteoarthritis (OA) indices into Korean (KWOMAC, KLequesne) and confirm their reliability, validity, and responsiveness.
The WOMAC and Lequesne indices were translated into Korean by three translators and translated back into English by three different translators. Fifty consecutive patients with OA were asked to rate the comprehensibility of the questions on a 4-point scale. The comprehensibility (responding with 'good' and 'very good') ranged from 78% to 99%. Test-retest was performed in another 47 patients with knee OA. The final 53 patients with knee OA, within the context of a clinical trial of two non-steroidal antiinflammatory drugs for 4 weeks, were studied to assess the internal consistency, construct validity, and responsiveness of the Korean versions.
The test-retest reliability of the KWOMAC 3 subscales and the KLequesne yielded intraclass correlation coefficients of 0.79-0.89 and 0.87. The Cronbach standardized alphas were 0.81-0.96 and 0.75, respectively. For the construct validity, the correlation coefficients of both the KWOMAC subscales and the KLequesne with patient pain assessment and patient global assessment were between 0.30 and 0.70 and the KWOMAC subscales correlated with the KLequesne (0.41-0.55). For responsiveness, the KWOMAC and KLequesne scores significantly improved by 4-week post-treatment compared with pre-treatment; effect size values were between 0.41 and 0.69 for the KWOMAC subscales and 0.70 for the KLequesne; and the relative efficiency values of the KWOMAC subscales vs the KLequesne were between 0.87 and 0.90.
The reliability, validity, and responsiveness of the KWOMAC and the KLequesne are confirmed.
The purpose was to describe the distribution of diagnoses among all referrals to a clinic specialized in temporomandibular disorders (TMD). A series of 1500 consecutive patients, evaluated by 1 dentist, were diagnosed according to the criteria of The International Classification of Diseases, 9th Revision, Clinical Modification: ICD-9-CM. Some referrals (12%) were never evaluated, were symptom-free, or were forwarded to other clinics. Various dental, neurogenic, occlusal, dentofacial, and other problems occurred. Vague orofacial pain was common, as was tension-type headache (6% each). More than 5% of the patients were affected by systemic disorders with manifestations in the temporomandibular joints. About half of all referrals could be strictly diagnosed with TMD. Myalgia was diagnosed as the main complaint in 19%. Internal derangement 'clicking' (15%) and 'closed lock' (6%) were more common than traumatic/ unspecified arthritis (6%) or osteoarthrosis (5%). A combination of myalgia and clicking appears to be the core sign in patients referred with TMD.
According to the data obtained during expert medical evaluation of the working capacity a considerable proportion among the examined accounts for patients with deforming osteoarthrosis (DOA), both primary and secondary. Despite the disease intensity and gravity of complications because of the development of compensatory processes most patients preserve work fitness for a long enough period of time, provided they are given proper work. To prevent the disease progress and grave disability, it is advisable that physicians engaged in the commissions for expert medical evaluation of the working capacity should prolong the time of temporary disability for more than 4 months, namely for the period of the development of compensation, provided the clinical and work fitness prognosis is favourable. Rehabilitation is also promoted by the use of concrete recommendations as to the specialized employment.
Osteoarthritis (OA), the most common form of arthritis, is a major contributor to functional impairment and loss of independence in older persons. The European Project on OSteoArthritis (EPOSA) is a collaborative study involving six European cohort studies on ageing. This project focuses on the personal and societal burden and its determinants of osteoarthritis. This paper describes the design of the project, and presents some descriptive analyses on selected variables across countries.
EPOSA is an observational study including pre-harmonized data from European cohort studies (Germany, Italy, the Netherlands, Spain, Sweden and the United Kingdom) on older community-dwelling persons aged 65 to 85 years. In total, 2942 persons were included in the baseline study with a mean age of 74.2 years (SD 5.1), just over half were women (51,9%). The baseline assessment was conducted by a face-to-face interview followed by a clinical examination. Measures included physical, cognitive, psychological and social functioning, lifestyle behaviour, physical environment, wellbeing and care utilisation. The clinical examination included anthropometry, muscle strength, physical performance and OA exam. A follow-up assessment was performed 12-18 months after baseline.
The EPOSA study is the first population-based study including a clinical examination of OA, using pre-harmonized data across European countries. The EPOSA study provides a unique opportunity to study the determinants and consequences of OA in general populations of older persons, including both care-seeking and non care-seeking persons.
Cites: Med Clin (Barc). 1999 Jun 5;112(20):767-7410422057
Mechanical load has been proposed as a risk factor for hand osteoarthritis. Dentists produce high manual forces in their work tasks. We studied whether the pattern of dental work tasks was associated with finger osteoarthritis. Radiographs of both hands of 291 middle-aged female dentists were examined for the presence of osteoarthritis. Patterns of dental work tasks during work history were empirically defined by cluster analysis. Three patterns emerged reflecting high, moderate, and mild task variation. Age, specialization, years in clinical work, various activities requiring hand use, family history of Heberden's nodes, body mass index, and smoking were accounted for in logistic regression analyses. The dentists with a history of low task variation had a greater prevalence of osteoarthritis in the thumb, index, and middle fingers compared with dentists with high variation (OR 2.22; 95%CI 1.04-4.91). The pattern of dental work task history is associated with the localization of osteoarthritis in the fingers.
Osteoarthritis (OA) is the most common human joint disease, characterized by loss and/or remodeling of joint synovium, cartilage, and bone. Here, we describe a genomewide linkage analysis of patients with idiopathic hand OA who were carefully phenotyped for involvement of either or both the distal interphalangeal (DIP) joints and the first carpometacarpal (CMC1) joints. The best linkage peaks were on chromosomes 4q and 3p and on the short arm of chromosome 2. Genomewide significance was reached for a locus on chromosome 2 for patients with affected CMC1 joints (LOD = 4.97); this locus was also significant for patients with OA in both CMC1 and DIP joints (LOD = 4.44). The peak LOD score at this locus coincides with a gene, MATN3, encoding the noncollagenous cartilage extracellular matrix protein, matrilin-3. Subsequent screening of the genomic sequence revealed a missense mutation, of a conserved amino acid codon, changing threonine to methionine in the epidermal growth factor-like domain in matrilin-3. The missense mutation cosegregates with hand OA in several families. The mutation frequency is slightly more than 2% in patients with hand OA in the Icelandic population and has a relative risk of 2.1.
In the county of Klaksvik, the Faroes, a simple hand test was used for screening all inhabitants between the ages of 40 and 74 years. With its high sensitivity and specificity it revealed a diagnostic panorama entirely different from that seen in previous investigations in other nordic countries. In Klaksvik the prevalence of hand handicap was about 40%, which is due to the high incidence of osteoarthrosis. The prevalence of rheumatoid arthritis was 1.1%. The high functional capacity and the lower occurrence of rheumatic nodules and erosions found in the patients with rheumatoid arthritis as compared with previous studies suggest that the disease takes a milder course in Klaksvik. This should support the hypothesis that RA patients benefit from a diet rich in fish.