Skin pentosidine in very early hip/knee osteoarthritis (CHECK) is not a strong independent predictor of radiographic progression over 5 years follow-up.

OBJECTIVES: Age-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced glycation end products (AGEs). The present study evaluates whether pentosidine can predict radiographic progression and/or burden over 5 years follow-up in a cohort of early knee and/or hip OA. DESIGN: The 5 years follow-up data of 300 patients from cohort hip & cohort knee (CHECK) were used. Radiographic progression and burden were assessed by X-rays of both knees and hips (Kellgren and Lawrence (K&L) and Altman scores). Baseline pentosidine levels (and urinary CTXII as a comparator) were measured by high-performance-liquid-chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA). Univariable and multivariable associations including baseline radiographic damage, age, gender, body mass index (BMI) and kidney function were performed. RESULTS: Both pentosidine and urinary C-terminal telopeptide of type II collagen (uCTXII) correlated with radiographic progression and burden. In general pentosidine did not have an added predictive value to uCTXII for progression nor burden of the disease. The best prediction was obtained for burden of radiographic damage (R(2) = 0.60-0.88), bus this was predominantly determined by baseline radiographic damage (without this parameter R(2) = 0.07-0.17). Interestingly, pentosidine significantly added to prediction of osteophyte formation, whereas uCTXII significantly added to prediction of JSN in multivariable analysis. CONCLUSION: Pentosidine adds to prediction of radiographic progression and burden of osteophyte formation and uCTXII to radiographic progression and burden of JSN, but overall skin pentosidine did not perform better that uCTXII in predicting radiographic progression or burden. Burden of damage over 5 years is mainly determined by radiographic joint damage at baseline.

Skin and urine pentosidine weakly correlate with joint damage in a cohort of patients with early signs of osteoarthritis (CHECK).

OBJECTIVES: Age-related changes in articular cartilage are likely to play a role in the aetiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced-glycation-endproducts (AGEs). Since, cartilage tissue is not readily available from patients for studying AGE levels, alternative approaches such as analyzing skin and urine are needed to study the role of cartilage AGE levels in OA. METHODS: Paired human skin and cartilage samples were obtained post mortem. Paired skin and urine samples were obtained from the CHECK cohort (early OA patients). Pentosidine levels were measured by high-performance liquid chromatography (HPLC). As marker of cumulative cartilage damage X-rays of both knees and hips were scored. Urinary CTXII (uCTXII) levels were measured, to assess current cartilage breakdown. RESULTS: Cartilage and skin pentosidine correlate well (R=0.473, P=0.05). Skin pentosidine was higher in mild (summed (Kellgren & Lawrence K&L) over four large joints ≥4) compared to no (summed K&L≤3) radiographic OA (P=0.007). Urinary pentosidine was not different between these two groups. Skin pentosidine levels were not related to cartilage breakdown (highest vs lowest tertile of uCTXII). Urinary pentosidine, however, was higher in the highest compared to the lowest uCTXII tertile (P=0.009). Multiple regression analysis showed age to be the only predictor of the summed K&L score and age, creatinine clearance and urinary pentosidine as predictors of uCTXII. CONCLUSION: The higher skin and urinary pentosidine levels in those with mild compared to no radiographic joint damage and low vs high cartilage breakdown respectively suggest that AGEs may contribute to disease susceptibility and/or progression. However, relations are weak and cannot be used as surrogate markers of severity of OA.

Functional capacity of people with early osteoarthritis: a comparison between subjects from the cohort hip and cohort knee (CHECK) and healthy ageing workers.

OBJECTIVE: The prevalence of osteoarthritis (OA) increases, but the impact of the disorder on peoples' functional capacity is not known. Therefore, the objective of this study was to compare self-reported health status and functional capacity of subjects with early OA of hip and/or knee to reference data of healthy working subjects and to assess whether this capacity is sufficient to meet physical job demands. METHODS: Self-reported health status and functional capacity of 93 subjects from the Cohort Hip and Cohort Knee (CHECK) were measured using the Short-Form 36 Health Survey and 6 tests of the Work Well Systems Functional Capacity Evaluation. Results were compared with reference data from 275 healthy workers, using t-tests. To compare the functional capacity with job demands, the proportions of subjects with OA performing lower than the p(5) of reference data were calculated. RESULTS: Compared to healthy workers, the subjects (mean age 56) from CHECK at baseline reported a significantly worse physical health status, whereas the women (n = 78) also reported a worse mental health status. On the FCE female OA subjects performed significantly lower than their healthy working counterparts on all 6 tests. Male OA subjects performed lower than male workers on 3 tests. A substantial proportion of women demonstrated functional capacities that could be considered insufficient to perform jobs with low physical demands. CONCLUSIONS: Functional capacity and self-reported health of subjects with early OA of the hips and knees were worse compared to healthy ageing workers. A substantial proportion of female subjects did not meet physical job demands.

Work participation and health status in early osteoarthritis of the hip and/or knee: a comparison between the Cohort Hip and Cohort Knee and the Osteoarthritis Initiative.

OBJECTIVE: To examine the work participation of Dutch people with early osteoarthritis (OA) in hips or knees and compare this with data from the American Osteoarthritis Initiative (OAI) cohort. The influence of health status and personal factors on work participation was analyzed. METHODS: In the Cohort Hip and Cohort Knee (CHECK) study, 1,002 subjects were included. Baseline questionnaire data from 970 subjects were analyzed. Rate ratios were calculated to compare work participation with the general Dutch population, after correcting (by stratifying) for age, sex, and education. Health status was measured using the Short Form 36 health survey and the Western Ontario and McMaster Universities Osteoarthritis Index. Groups were compared (CHECK versus OAI, workers versus nonworkers) using t-tests. RESULTS: The mean age of the subjects was 56 years and 79% were women. Overall participation was 51%, similar to the general Dutch population and lower than in the OAI (76%). Point prevalence of sick leave because of hip/knee symptoms was 2%, and year prevalence was 12%. Of the subjects, 14% had made work adaptations. Workers reported significantly better health status (corrected for age, sex, and education) than nonworkers. CONCLUSION: Work participation of Dutch people with early OA is similar to the general population and significantly lower than American subjects. Increasing age, female sex, and lower education level were related to lower participation. Societal factors appear to have had more effect on work participation than health status in this stage of OA. The better health status of workers could not be explained solely by selection bias, but may be a result of work.

Serum and urinary biochemical markers for knee and hip-osteoarthritis: a systematic review applying the consensus BIPED criteria.

CONTEXT: Molecules that are released into biological fluids during matrix metabolism of articular cartilage, subchondral bone, and synovial tissue could serve as biochemical markers of the process of osteoarthritis (OA). Unfortunately, actual breakthroughs in the biochemical OA marker field are limited so far. OBJECTIVE: By reviewing the status of commercially available biochemical OA markers according to the "Burden of disease, Investigative, Prognostic, Efficacy of intervention, and Diagnostic" ("BIPED") classification, future use of this "BIPED" classification is encouraged and more efficient biochemical OA marker research stimulated. DATA SOURCES: Three electronic databases [PubMed, Scopus, EMBASE (1997-May 2009)] were searched for publications on blood and urinary biochemical markers in human primary knee and hip-OA. STUDY SELECTION: Stepwise selection of original English publications describing human studies on blood or urinary biochemical markers in primary knee or hip-OA was performed. Selected articles were fully read to determine whether biochemical markers were investigated on performance within any of the "BIPED" categories. Eighty-four relevant publications were identified. DATA EXTRACTION: Data from relevant publications were tabulated according to the "BIPED" classification. Individual analyses within a publication were summarized in general "BIPED" scores. DATA SYNTHESIS: An uneven distribution of scores on biochemical marker performance and heterogeneity among the publications complicated direct comparison of individual biochemical markers. Comparison of categories of biochemical markers was therefore performed instead. In general, biochemical markers of cartilage degradation were investigated most extensively and performed well in comparison with other categories of biochemical markers. Biochemical markers of bone metabolism performed less adequately. Biochemical markers of synovial tissue metabolism were not investigated extensively, but performed quite well. CONCLUSIONS: Specific biochemical markers and categories of biochemical markers as well as their nature, origin and metabolism, need further investigation. International standardization of future investigations should be pursued to obtain more high-quality, homogenous data on the full spectrum of biochemical OA markers.

CHECK (Cohort Hip and Cohort Knee): similarities and differences with the Osteoarthritis Initiative.

OBJECTIVE: To describe the osteoarthritis study population of CHECK (Cohort Hip and Cohort Knee) in comparison with relevant selections of the study population of the Osteoarthritis Initiative (OAI) based on clinical status and radiographic parameters. METHODS: In The Netherlands a prospective 10-year follow-up study was initiated by the Dutch Arthritis Association on participants with early osteoarthritis-related complaints of hip and/or knee: CHECK. In parallel in the USA an observational 4-year follow-up study, the OAI, was started by the National Institutes of Health, on patients with or at risk of symptomatic knee osteoarthritis. For comparison with CHECK, the entire cohort and a subgroup of individuals excluding those with exclusively hip pain were compared with relevant subpopulations of the OAI. RESULTS: At baseline, CHECK included 1002 participants with in general similar characteristics as described for the OAI. However, significantly fewer individuals in CHECK had radiographic knee osteoarthritis at baseline when compared with the OAI (p<0.001). In contrast, at baseline, the CHECK cohort reported higher scores on pain, stiffness and functional disability (Western Ontario and McMaster osteoarthritis index) when compared with the OAI (all p<0.001). These differences were supported by physical health status in contrast to mental health (Short Form 36/12) was at baseline significantly worse for the CHECK participants (p<0.001). CONCLUSION: Although both cohorts focus on the early phase of osteoarthritis, they differ significantly with respect to structural (radiographic) and clinical (health status) characteristics, CHECK expectedly representing participants in an even earlier phase of disease.

[Alendronate more effective than alfacalcidol in the prevention of osteoporosis in patients with rheumatic disease who are starting glucocorticoid therapy]. / Alendroninezuur effectiever dan alfacalcidol voor preventie van osteoporose bij patiënten met een reumatische ziekte die starten met glucocorticoïdtherapie.

OBJECTIVE: To compare the effects of alendronate and alfacalcidol in the prevention ofglucocorticoid-related osteoporosis in patients with a rheumatic disease. DESIGN: Randomised, double-blind, double-placebo clinical trial (www. clinicaltrials.gov; number: NCT00138983). METHODS: A total of 201 patients with rheumatic disease who were starting glucocorticoid treatment at a daily dose that was equivalent to at least 7.5 mg of prednisone were randomised to alendronate (10 mg) and a placebo capsule ofalfacalcidol daily (n = 100) or alfacalcidol (1 microg) and a placebo tablet ofalendronate daily (n = 101) for 18 months. Primary outcome was change in lumbar spine bone mineral density at 18 months. The main secondary outcome was the incidence of morphometrically confirmed vertebral deformities. RESULTS: Overall, 163 patients completed the study. The bone mineral density of the lumbar spine increased by 2.1% (95% CI: 1.1-3.1) in the alendronate group and decreased by 1.9% (95% CI: -3.I--0.7) in the alfacalcidol group. At 18 months the mean difference in change in bone mineral density between the two groups was 4.0% (95% CI: 2.4-5-5). Three patients in the alendronate group had a new vertebral deformity, compared with 8 patients in the alfacalcidol group, including 5 symptomatic vertebral fractures in 3 patients; the hazard ratio was 0.4 (95% CI: 0.1-1.4). CONCLUSION: Alendronate was more effective than alfacalcidol in preventing glucocorticoid-induced bone loss during this 18-month trial in patients with rheumatic diseases who were starting glucocorticoid treatment.