Glucosamine sulfate. (57/3950)

Glucosamine sulfate's role in halting or reversing joint degeneration appears to be directly due to its ability to act as an essential substrate for, and to stimulate the biosynthesis of, the glycosaminoglycans and the hyaluronic acid backbone needed for the formation of the proteoglycans found in the structural matrix of joints. Successful treatment of osteoarthritis must effectively control pain and should slow down or reverse the progression of the degeneration. Biochemical and pharmacological data combined with animal and human studies demonstrate that glucosamine sulfate is capable of satisfying both of these criteria.  (+info)

Involvement of thioredoxin in rheumatoid arthritis: its costimulatory roles in the TNF-alpha-induced production of IL-6 and IL-8 from cultured synovial fibroblasts. (58/3950)

Thioredoxin (TRX) is a cellular reducing catalyst induced by oxidative stress and is involved in the redox regulation of transcription factors such as NF-kappaB. We found that the serum TRX concentration was elevated in patients with rheumatoid arthritis (RA) as compared with values from healthy individuals and patients with osteoarthritis (33.6 +/- 35.1 vs 11.8 +/- 6.6 ng/ml, p < 0.01). Moreover, the TRX concentration in the synovial fluid (SF) was much more elevated in RA patients than in osteoarthritis patients (103.4 +/- 53.3 vs 24.6 +/- 17.4 ng/ml, p < 0.001). Multiple regression analysis revealed that the serum C-reactive protein value was better correlated with the linear combination of SF TNF-alpha and SF TRX values than with SF TNF-alpha alone, suggesting that TRX might play a subsidiary role in the rheumatoid inflammation. We thus examined the effect of TRX on the TNF-alpha-induced IL-6 and IL-8 production using rheumatoid synovial fibroblast cultures. The extents of IL-6 and IL-8 production in response to TNF-alpha were greatly augmented by TRX as compared with TNF-alpha alone. TRX alone did not have such effects. We also found that TRX appeared to accelerate the nuclear translocation of NF-kappaB, a major transcriptional regulator for production of IL-6 and IL-8 on stimulation with TNF-alpha. Consistent with these findings, the IkappaBalpha phosphorylation at Ser32 and its subsequent degradation in response to TNF-alpha was facilitated by TRX. These findings indicate that the elevated TRX concentration in SF of RA patients might be involved in the aggravation of rheumatoid inflammation by augmenting the NF-kappaB activation pathway.  (+info)

Measurement of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in patients with knee osteoarthritis: comparison with generalized osteoarthritis. (59/3950)

OBJECTIVES: To compare plasma levels of matrix metalloproteinase (MMP)-3, MMP-9 and tissue inhibitor of metalloproteinases-1 (TIMP-1) between patients with knee osteoarthritis and normal subjects, to investigate whether the degree of knee joint involvement is related to those measurements, and to compare patients with and without generalized osteoarthritis. METHODS: Eighty-three women with knee osteoarthritis (OA patients) were studied. Plasma levels of MMP-3, MMP-9 and TIMP-1 were measured by enzyme immunoassays. Knee and hand radiographs were taken of all patients. The joints of the knee and hand were graded from 0 to 4 according to Kellgren and Lawrence criteria. All OA patients were divided into a generalized OA (GOA) group (n = 37) and a knee OA (KOA) group (n = 46) according to Doherty's criteria. MMPs and TIMP were also measured in 19 normal subjects. RESULTS: Plasma levels of MMP-3 and TIMP-1 were significantly higher in OA patients than in normal subjects. In contrast, MMP-9 was lower in OA patients than in normal subjects. Plasma levels of MMP-3 and MMP-9 were not influenced by the grade of knee OA. TIMP-1 was influenced by the grade of knee OA. Plasma levels of MMP-3 were significantly elevated in GOA compared to KOA. In contrast, there were no significant differences in plasma levels of MMP-9 and TIMP-1 between GOA and KOA. CONCLUSION: Since the plasma level of MMP-3 in GOA was higher than that in KOA patients, it may be a superior indicator for whole-joint degeneration.  (+info)

Tramadol allows reduction of naproxen dose among patients with naproxen-responsive osteoarthritis pain: a randomized, double-blind, placebo-controlled study. (60/3950)

OBJECTIVE: To demonstrate that in patients receiving naproxen for the pain of osteoarthritis (OA), the addition of tramadol will allow a reduction in the naproxen dosage without compromising pain relief. METHODS: This trial consisted of a 5-week open-label run-in and an 8-week double-blind phase. Patients with at least moderate pain (> or =40 mm on a 100-mm visual analog scale) of OA of the knee after a 1-week medication washout were treated with naproxen 500 mg/day for 1 week. Patients whose pain scores were reduced to <20 mm were discontinued. The remaining patients received naproxen 1,000 mg/day for 3 weeks. Tramadol 200 mg/day was added during the third week. Patients were then randomized in a double-blind manner to continue tramadol 200 mg/day or to begin placebo in addition to naproxen. Randomization was stratified based on response to naproxen 1,000 mg/day. During the double-blind phase, the naproxen dose was reduced by 250 mg every 2 weeks. The primary efficacy end point was the minimum effective naproxen dose (MEND). The MEND was defined as 250 mg above the naproxen daily dosage at which pain relief was no longer adequate. Patients discontinuing the double-blind phase of the study for reasons other than lack of efficacy were assigned a MEND equal to the last naproxen dose received. If the effect of treatment between the responder and nonresponder groups was statistically different, the difference in the MEND was assessed separately within the groups. RESULTS: Of 236 patients randomized (mean age 61 years; 147 females), 90 were stratified as naproxen responders and 146 as naproxen nonresponders. There was a significant difference (P = 0.040) in the treatment effect between the naproxen responders and nonresponders, thus demonstrating a difference in the way responders and nonresponders react to a decrease in naproxen dosage after the addition of tramadol. Among naproxen responders, the MEND was significantly lower in patients receiving tramadol (n = 36) than in patients receiving placebo (n = 54), 221 mg versus 407 mg, respectively (P = 0.021). For the naproxen nonresponders, the mean MEND was 419 mg in the tramadol group and 396 mg in the placebo group (P = 0.706). CONCLUSION: In patients with painful OA of the knee responding to naproxen 1,000 mg/day, the addition of tramadol 200 mg/day allows a significant reduction in the dosage of naproxen without compromising pain relief.  (+info)

Osteoarthritis and risk of falls, rates of bone loss, and osteoporotic fractures. Study of Osteoporotic Fractures Research Group. (61/3950)

OBJECTIVE: To examine the association between osteoarthritis (OA), as defined by radiographic evidence and self report, and osteoporotic fractures, falls, and bone loss in a cohort of elderly white women. METHODS: A cohort of 5,552 elderly women from the Study of Osteoporotic Fractures was followed up prospectively for a mean of 7.4 years. Self-reported, physician-diagnosed OA was recorded at interview, and radiologic OA of the hip and hand were defined from pelvis and hand radiographs obtained at baseline by validated techniques. Prevalent and incident vertebral fractures were detected by vertebral morphometry, and data on incident fractures and falls were collected by postcard surveys; fractures were confirmed by radiography. Bone mineral density (BMD) was measured on 2 occasions at the hip, lumbar spine, and calcaneus, and rates of bone loss were calculated. RESULTS: Women with radiographic hip OA had a reduced risk of recurrent falls in the first year (relative risk [RR] 0.7, 95% confidence interval [95% CI] 0.5-0.95). However, those with self-reported OA had an increased risk of falls (RR 1.4, 95% CI 1.2-1.5). Radiographic hip OA was associated with reduced bone loss in the femoral neck compared with controls (mean +/- SD -0.29+/-0.09%/year versus -0.51+/-0.03%/year; P = 0.018). However, radiographic hip OA showed nonsignificant trends toward increased bone loss at the calcaneus and lumbar spine. There was no significant association between self-reported OA or radiographic hand OA with bone loss. No definition of OA was associated with incident nonvertebral fracture, hip fracture, or vertebral fracture. CONCLUSION: Despite having increased BMD compared with controls, subjects with OA did not have a significantly reduced risk of osteoporotic fracture, although there was a trend toward a reduced risk of femoral neck fractures in subjects with severe radiographic OA. The failure of the observed increase in BMD to translate into a reduced fracture risk may be due, in part, to the number and type of falls sustained by subjects with OA. Patients with OA should not be considered to be at a lower risk of fracture than the general population. Physicians should be aware that a high BMD in patients with OA may be falsely reassuring.  (+info)

Reexpression of type IIA procollagen by adult articular chondrocytes in osteoarthritic cartilage. (62/3950)

OBJECTIVE: To test for the reexpression of the chondroprogenitor splice variant of the gene COL2A1, type IIA procollagen (containing a cysteine-rich NH2 propeptide), in adult articular chondrocytes in osteoarthritic (OA) joint disease. METHODS: In situ hybridization and immunohistochemical localization were performed on normal and OA articular cartilage specimens. The presence of type IIA procollagen messenger RNA (mRNA) expression was confirmed by Northern blot analysis. RESULTS: In normal articular cartilage, no expression of mRNA or presence of type IIA procollagen was found. In OA articular cartilage, focally intense staining for type IIA protein was detected. Consistent with this, chondrocytes, particularly in the middle zones of articular cartilage, expressed type IIA procollagen mRNA. OA repair cartilage typically showed a broad zone of cells expressing type IIA mRNA and protein. CONCLUSION: Type IIA procollagen is reexpressed by adult articular chondrocytes in OA cartilage degeneration, indicating the potential reversion of the cells to a chondroprogenitor cellular phenotype. The absence of type IIA mRNA and protein in normal adult articular cartilage and its onset in the diseased state suggests type IIA procollagen as a marker of OA.  (+info)

C-telopeptide pyridinoline cross-links. Sensitive indicators of periodontal tissue destruction. (63/3950)

C-telopeptides and related pyridinoline cross-links of bone Type I collagen are sensitive markers of bone resorption in osteolytic diseases such as osteoporosis and osteoarthritis. We have studied the release of C-telopeptide pyridinoline crosslinks of Type I collagen as measures of bone destruction in periodontal disease. Studies in preclinical animal models and humans have demonstrated the relationship between radiographic bone loss and crevicular fluid C-telopeptide levels. We have recently found that C-telopeptide levels correlate strongly with microbial pathogens associated with periodontitis and around endosseous dental implants. Host-modulation of bone-related collagen breakdown has been shown by studies in humans demonstrating that MMP inhibition blocks tissue destruction and release of C-telopeptides in patients with active periodontal disease.  (+info)

The influence of tissue cross-talking on OA progression: role of nonsteroidal antiinflammatory drugs. (64/3950)

Osteoarthritis is increasingly recognized as a complex illness in which interrelationships between the different tissues of the joint are important. We are still some way from a complete understanding of the pathophysiologic and temporal relationships between bone, synovial tissue and cartilage. Recent evidence points to a significant role for cytokines and growth factors in osteoarthritis that leads to a preponderance of catabolic processes in the joint. In-vitro culture of human cartilage has been used as a model to measure the effects of drugs used in the treatment of osteoarthritis on anabolic and catabolic processes. On this basis, the nonsteroidal antiinflammatory drugs can be categorized into one of three classes depending on whether they are inhibitory (e.g., indomethacin and naproxen), neutral (e.g., diclofenac, aspirin and piroxicam) or stimulatory (e.g., aceclofenac, tenidap and tolmetin) of glycosaminoglycan synthesis in chondrocytes. The marked differences between these nonsteroidal antiinflammatory drugs suggest that a mechanism other than cyclooxygenase inhibition is involved in their effects on glycosaminoglycan synthesis. Inhibition of IL-1beta and the stimulation of growth factors are suggested as possible mechanisms. Although the significance of these properties of nonsteroidal antiinflammatory drugs awaits confirmation in in-vivo and clinical situations, they do provide the clinician with a new parameter with which to choose therapy in osteoarthritis.  (+info)