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WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, Malaga, SPAIN, APR 14-17, 2016; International audience

Udgivelsesdato: 2009-Mar

To determine the efficacy and safety of risedronate in patients with knee osteoarthritis (OA), the British study of risedronate in structure and symptoms of knee OA (BRISK), a 1-year prospective, double-blind, placebo-controlled study, enrolled patients (40–80 years of age) with mild to moderate OA of the medial compartment of the knee. The primary aims were to detect differences in symptoms and function. Patients were randomized to once-daily risedronate (5 mg or 15 mg) or placebo. Radiographs were taken at baseline and 1 year for assessment of joint-space width using a standardized radiographic method with fluoroscopic positioning of the joint. Pain, function, and stiffness were assessed using the Western Ontario and McMaster Universities (WOMAC) OA index. The patient global assessment and use of walking aids were measured and bone and cartilage markers were assessed. The intention-to-treat population consisted of 284 patients. Those receiving risedronate at 15 mg showed improvement of the WOMAC index, particularly of physical function, significant improvement of the patient global assessment (P < 0.001), and decreased use of walking aids relative to patients receiving the placebo (P = 0.009). A trend towards attenuation of joint-space narrowing was observed in the group receiving 15 mg risedronate. Eight percent (n = 7) of patients receiving placebo and 4% (n = 4) of patients receiving 5 mg risedronate exhibited detectable progression of disease (joint-space width ≥ 25% or ≥ 0.75 mm) versus 1% (n = 1) of patients receiving 15 mg risedronate (P = 0.067). Risedronate (15 mg) significantly reduced markers of cartilage degradation and bone resorption. Both doses of risedronate were well tolerated. In this study, clear trends towards improvement were observed in both joint structure and symptoms in patients with primary knee OA treated with risedronate.\ud

Objective. To investigate in a randomized clinical trial setting with an aggressive combination-therapy arm and a mild-monotherapy arm, whether therapy-induced changes in urinary C-terminal crosslinking telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) predict 5-year radiographic progression in patients with rheumatoid arthritis (RA). Methods. Patients had participated in the COBRA (Combinatietherapie Bij Reumatoïde Artritis) trial comparing aggressive step-down combination therapy (the COBRA regimen, including temporary high-dose prednisolone, temporary low-dose methotrexate, and sulfasalazine [SSZ]) and mild monotherapy (SSZ). Urinary CTX-I and CTX-II levels were measured at baseline and 3, 6, 9, and 12 months after initiation of treatment. Radiographs were scored according to the modified Sharp/van der Heijde method (mean of 2 independent readers who were aware of the sequence). Individual long-term radiographic progression was estimated, using baseline radiographs and all radiographs obtained during the followup period, by simple linear regression analysis (curve fitting). Results. Both COBRA therapy and SSZ monotherapy produced a significant decrease in urinary CTX-I and CTX-II levels at 3 months, and this decrease was amplified at 6 months. COBRA therapy suppressed CTX-II (change from baseline levels -36% and -43% at 3 and 6 months, respectively), but not CTX-I, significantly better than did SSZ (-17% and -21% at 3 and 6 months, respectively) at 3 and 6 months. The magnitude of the decrease in urinary CTX-II levels at 3 months significantly predicted long-term (5-year) radiographic progression (β = 0.48 [95% confidence interval (95% CI) 0.13, 0.83]). This effect was independent of the change in disease activity and inflammation indices at 3 months. Patients whose CTX-II levels were normalized (

The progression of rheumatoid arthritis (RA), a disease characterized by synovitis, cartilage degradation and bone erosion, is highly variable from patient to patient. New specific biological markers reflecting quantitative and dynamic changes in joint tissue turnover have been recently developed and include assays for type II collagen synthesis and degradation and synovitis. Increasing evidence from prospective studies in early RA indicate that some of these markers may be useful to predict the progression and identify patients at risk for rapid joint damage, before any damage is detected by radiography. Although studies on their value in assessing the efficacy of treatments are still limited, preliminary data in early RA suggest that biological markers will play an important role in the development and the early monitoring of disease modifying antirheumatic drugs with respect to future radiographic progression

In order to validate a new technique to measure bone mineral density (BMD) of the forearm with a single X-ray absorptiometry device (DTX 100), we have measured the BMD of 195 women, aged 32 to 83 years, free of metabolic bone disease, simultaneously on two devices: 1. BMD of the ultradistal radius and of the distal radius and ulna on DTX 100, Osteometer, 2. BMD of the lumbar spine, of the proximal femur, of the whole body and of the distal and ultradistal radius by dual X-ray absorptiometry (DXA) on an Hologic 2000 device. The precision of DTX, assessed by 5 repeated measurements on 9 volunteers, was 1% for the distal site and 2% for the ultradistal site. There was a high correlation (r = 0.93) between radial BMD measurement by DTX and Hologic 2000. Correlations between forearm BMDs measured by DTX and whole body BMD were as high (r = 0.80-0.82) as between whole body BMD and lumbar spine (r = 0.82), femoral neck (r = 0.77) and femoral trochanter (r = 0.76). Age-related bone loss measured by DTX was 27% and 31% at the distal and ultra distal radius respectively, as compared to 17% for the lumbar spine, 21% for the femoral neck and 16% for the whole body BMD. In a group of 20 untreated osteoporotic women with vertebral fractures, forearm BMD was as sensitive (T score of -3.1 and -2.9 for distal and ultra distal) as was lumbar spine (T = -2.9) and femoral neck (T = -2.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Context: Proteolytic fragments of chromogranin A (CgA) including the CgA 1-76 fragment (called vasostatin-I [VS-I]) could be a useful biomarker of sepsis, but there is no available immunoassay. Methods: A sandwich ELISA for VS-I was developed, and plasma VS-I was measured in 30 healthy controls and 60 critically ill patients with sepsis. Results: The ELISA showed intra- and inter-assay coefficients of variations (CVs) below 4 and 9%. Plasma VS-I was significantly increased compared with controls in patients with sepsis, severe sepsis, and sepsis shock (p < 0.0001). Receiver operating curve (ROC) analyses indicated that plasma VS-I was more sensitive and specific than plasma CgA to diagnose sepsis and to assess its severity. Conclusions: The measurements of plasma VS-I with this new ELISA may be useful for the clinical investigation of patients with sepsis.

UNLABELLED: The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommend that a marker of bone formation (serum procollagen type I N propeptide, s-PINP) and a marker of bone resorption (serum C-terminal telopeptide of type I collagen, s-CTX) are used as reference analytes for bone turnover markers in clinical studies. INTRODUCTION: Bone turnover markers (BTM) predict fracture risk, and treatment-induced changes in specific markers account for a substantial proportion of fracture risk reduction. The aims of this report were to determine their clinical potential in the prediction of fracture risk and for monitoring the treatment of osteoporosis and to set an appropriate research agenda. METHODS: Evidence from prospective studies was gathered through literature review of the PUBMED database between the years 2000 and 2010 and the systematic review of the Agency for Healthcare Research and Quality up to 2001. RESULTS: High levels of BTMs may predict fracture risk independently from bone mineral density in postmenopausal women. They have been used for this purpose in clinical practice for many years, but there is still a need for stronger evidence on which to base practice. BTMs provide pharmacodynamic information on the response to osteoporosis treatment, and as a result, they are widely used for monitoring treatment in the individual. However, their clinical value for monitoring is limited by inadequate appreciation of the sources of variability, by limited data for comparison of treatments using the same BTM and by inadequate quality control. IOF/IFCC recommend one bone formation marker (s-PINP) and one bone resorption marker (s-CTX) to be used as reference markers and measured by standardised assays in observational and intervention studies in order to compare the performance of alternatives and to enlarge the international experience of the application of markers to clinical medicine. CONCLUSION: BTM hold promise in fracture risk prediction and for monitoring treatment. Uncertainties over their clinical use can be in part resolved by adopting international reference standards.