Biomedical subjects

Changhai Ding

Publications and source records attributed to Changhai Ding.

29 records · Page 2Linked to original sources

PubMed2005

Knee structural alteration and BMI: a cross-sectional study.

OBJECTIVE: To describe the associations among BMI, knee cartilage morphology, and bone size in adults. RESEARCH METHODS AND PROCEDURES: A cross-sectional convenience sample of 372 male and female subjects (mean age, 45 years; range, 26 to 61 years) was studied. Knee articular cartilage defect score (0 to 4) and prevalence (defect score of >/=2), volume, and thickness, as well as bone surface area and/or volume, were determined at the patellar, tibial, and femoral sites using T1-weighted fat-saturation magnetic resonance imaging. Height, weight, BMI, and radiographic osteoarthritis were measured by standard protocols. RESULTS: In multivariate analysis in the whole group, BMI was significantly associated with knee cartilage defect scores (beta: +0.016/kg/m(2) to +0.083/kg/m(2), all p < 0.05) and prevalence (odds ratio: 1.05 to 1.12/kg/m(2), all p < 0.05 except for the lateral tibiofemoral compartment). In addition, BMI was negatively associated with patellar cartilage thickness only (beta = -0.021 mm/kg/m(2); p = 0.039) and was positively associated with tibial bone area (medial: beta = +7.1 mm(2)/kg/m(2), p = 0.001; lateral: beta = +3.2 mm(2)/kg/m(2), p = 0.037). Those who were obese also had higher knee cartilage defect severity and prevalence and larger medial tibial bone area but no significant change in cartilage volume or thickness compared with those of normal weight. DISCUSSION: This study suggests that knee cartilage defects and tibial bone enlargement are the main structural changes associated with increasing BMI particularly in women. Preventing these changes may prevent knee osteoarthritis in overweight and obese subjects.

Adult↗

PubMed2005

The genetic contribution and relevance of knee cartilage defects: case-control and sib-pair studies.

OBJECTIVE: To describe the differences in knee cartilage defects between offspring of subjects with at least one parent with a total knee replacement for severe primary knee osteoarthritis (OA) and controls; and to estimate the heritability of knee cartilage defects in sib-pairs. METHODS: Population based, case-control study of 186 matched pairs (mean age 45 yrs, range 26-61) and sib-pair study of 128 subjects from 51 families (115 sib-pairs) within the case-control study. Knee cartilage defect scores (0-4) and prevalence (a cartilage defect score > or = 2) were assessed at the patellar, tibial, and femoral sites by processing images acquired using T1 weighted fat-saturated magnetic resonance imaging. Heritability was estimated using the SOLAR genetic analysis program. RESULTS: The prevalence of knee cartilage defects was surprisingly high (50% scored > or = 2 in any site). Compared to controls, offspring had higher knee cartilage defect scores and prevalence in tibiofemoral (4.39 vs 4.01, p = 0.003; 41% vs 28%, p = 0.009), patellar (1.32 vs 1.10, p = 0.031; 35% vs 26%, p = 0.075), and whole (5.71 vs 5.10, p = 0.002; 57% vs 42%, p = 0.007) compartments. These all became nonsignificant after adjustment for knee pain and radiographic OA. In the sib-pair component, knee cartilage defects had heritability for scores and prevalence, respectively, of 38% (p = 0.072) and 47% (p = 0.082) for tibiofemoral, 52% (p = 0.009) and 78% (p = 0.025) for patellar, and 43% (p = 0.038) and 68% (p = 0.072) for the whole compartments. These estimates became weaker at tibiofemoral and whole compartments after adjustment for bone size, knee pain, and radiographic OA. CONCLUSION: Knee cartilage defects are common, have a genetic component that is linked to the genetic contribution to knee pain and bone size, and may have a role in the genetic pathogenesis of knee OA.

Adult↗

PubMed2004

The genetic contribution to muscle strength, knee pain, cartilage volume, bone size, and radiographic osteoarthritis: a sibpair study.

OBJECTIVE: To estimate the heritability of muscle strength, knee pain, cartilage volume, bone size, and radiographic osteoarthritis (ROA), and to assess whether heritability of the knee structural components is independent of ROA. METHODS: A sibpair design was utilized. Sagittal T1-weighted fat-suppressed magnetic resonance imaging (MRI) of the right knee was performed to determine cartilage volume and bone size. Standing semiflexed radiographs of the same knee were obtained to assess the presence of ROA. Knee pain was assessed by questionnaire and muscle strength by dynamometry. Heritability was estimated using the genetic analysis program SOLAR. RESULTS: A total of 128 subjects (61 men, 67 women; mean age 45 years) from 51 families representing 115 sibpairs were studied. Lower limb muscle strength had high heritability (42%; P = 0.02), as did knee pain (44%; P = 0.07). Heritability estimates for cartilage volume were 65% for medial tibial cartilage, 77% for lateral tibial cartilage, and 84% for patellar cartilage, and heritability estimates for bone size were 85% for medial tibial bone area, 57% for lateral tibial bone area, and 70% for patella bone volume (all P < or = 0.004). For ROA, heritability was 61% for presence (with a large standard error) (P = 0.16) and 61% for severity (P = 0.02). The estimates for tibial bone areas were the only ones markedly reduced after adjustment for body size, while all estimates with the exception of knee pain were independent of ROA. Cartilage and, to a lesser extent, bone sites investigated by MRI were largely under independent genetic control, with a lesser shared genetic component. CONCLUSION: With the exception of prevalent ROA, all knee modalities assessed had high heritability, most likely reflecting a strong genetic component. Cartilage volume, bone size, and muscle strength all have the potential to be studied in quantitative trait linkage analyses, but their exact relevance with regard to OA remains uncertain at this time.

Adult↗

PubMed2004

Early radiographic osteoarthritis is associated with substantial changes in cartilage volume and tibial bone surface area in both males and females.

OBJECTIVE: To describe the association between early radiographic osteoarthritis of the knee (ROA), knee cartilage volume and tibial bone surface area. METHODS: Cross-sectional convenience sample of 372 male and female subjects (mean age 45 years, range 26-61). Articular cartilage volume, bone area and volume were determined at the patella, medial tibial and lateral tibial compartments by processing images acquired in the sagittal plane using T1-weighted fat saturation MRI. ROA was assessed with a standing semiflexed radiograph and the OARSI atlas for joint space narrowing and osteophytosis. Both radiographs and MRIs were performed in the right knee and read by different observers. RESULTS: ROA (predominantly grade 1) was present in 17% of subjects of which medial joint space narrowing was most common (14%) followed by medial osteophytes (6%). Grade one medial joint space narrowing was associated with substantial reductions in cartilage volume at both the medial and lateral tibial and patellar sites within the knee (adjusted mean difference 11-13%, all P<0.001) while grade one osteophytosis was associated with substantial increases in both lateral and medial tibial joint surface area (adjusted mean difference 10-16%, all P<0.001). In contrast, osteophytosis was not associated with a significant change in cartilage volume and joint space narrowing was not associated with a significant change in tibial bone area (all P>0.05). CONCLUSIONS: Early medial compartment ROA is associated with substantial reductions in cartilage volume and increases in bone area. These large changes, when combined with similar measurement error for MRI and radiographs, suggest that MRI may be superior at detecting and hence understanding early osteoarthritis of the knee in humans.

Adult↗

PubMed2004

Bertilimumab Cambridge Antibody Technology Group.

Cambridge Antibody Technology (CAT) is developing bertilimumab, an anti-eotaxin-1 monoclonal antibody, for the potential treatment of allergic disorders. By September 2003, CAT had released results from phase I/II trials, and was seeking to outlicense rights for bertilimumab.

Animals↗

PubMed2003

Knee articular cartilage development in children: a longitudinal study of the effect of sex, growth, body composition, and physical activity.

The aim of this study was to describe the effect of sex, growth, Tanner stage, and physical activity on knee articular cartilage volume development. A total of 74 randomly selected male and female children aged 9-18 y were measured on two occasions at an average interval of 1.6 y (range 1.3-1.9). Articular cartilage volume was determined at the patella, medial tibial, and lateral tibial compartments by processing images acquired in the sagittal plane using T1-weighted fat saturation magnetic resonance. Height, weight, and BMI were measured while Tanner stage and physical activity were assessed by questionnaire. Articular cartilage volume increased at all sites peaking in Tanner stage two. Males gained articular cartilage faster than females at all sites (patella +233 microL/y, 95% CI -7, +473, medial tibial +350 microL/y, 95% CI +118, +582, lateral tibial +256 microL/y, 95% CI +22, +488). In both sexes, articular cartilage volume accrual at tibial but not patella sites correlated significantly with height change but not weight change. Overweight children did not differ significantly from normal children in articular cartilage volume either cross-sectionally or longitudinally. The most consistent physical activity association was with average intensity of sport with those above the median gaining approximately twice as much as those below the median at tibial (p < 0.05) but not patella sites. In conclusion, most children gain articular cartilage during growth, but there is wide variation in the amount of articular cartilage accrual. In particular, younger children, males, and those undertaking more vigorous sports have substantially higher accrual rates. These results provide novel data on articular cartilage development in humans. The long-term significance of these results with regard to osteoarthritis of the knee in later life remains hypothetical.

Adolescent↗

PubMed2003

Technology evaluation: MRA, Chugai.

Chugai, the Japanese subsidiary of Roche, is developing a humanized anti-interleukin (IL)-6 receptor monoclonal antibody MRA for the potential treatment of multiple myeloma, rheumatoid arthritis, Crohn's disease and other IL-6-related disorders. MRA is currently undergoing phase II clinical trials for these indications.

Antibodies, Monoclonal↗

PubMed2003

Licofelone (Merckle).

EuroAlliance (a consortium of Alfa Wassermann SpA, Lacer SA and Merckle GmbH) is developing licofelone, a dual cyclooxygenase and 5-lipoxygenase inhibitor for the potential treatment of inflammatory disorders including osteoarthritis.

Acetates↗

PubMed2003

Leflunomide, a new disease-modifying drug for treating active rheumatoid arthritis in methotrexate-controlled phase II clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of leflunomide in comparison with methotrexate (MTX) on patients with rheumatoid arthritis (RA) in China. METHODS: Five hundred and sixty-six patients with active rheumatoid arthritis were randomly assigned to receive leflunomide at 20 mg once daily or MTX at 15 mg once weekly in a controlled trial. Five hundred and four patients completed the 12-week treatment and some patients continued the treatment for 24 weeks. RESULTS: Both leflunomide and MTX could improve the symptoms, signs, and joint function, but there were no changes in X-ray observations of patients with rheumatoid arthritis. In the leflunomide group, the overall rates of effectiveness at 12 weeks and 24 weeks were 86.94% and 92.31% respectively; the rates of remarkable improvement were 64.95% and 79.81% respectively. In the MTX group, the overall rates of effectiveness at 12 weeks and 24 weeks were 84.04% and 83.15% respectively; the rates of remarkable improvement were 56.81% and 75.28% respectively. According to intent-to-treat analysis, the ACR 20% response rates at 12 weeks and 24 weeks in the leflunomide group were 62.54% and 67.18% respectively, compared with 60.08% and 61.32% respectively in MTX group. No statistical differences were shown in the efficacy between the two groups (P > 0.05). The adverse events in the leflunomide group were gastrointestinal symptoms, skin rash, alopecia, nervous system symptoms, decreased leukocyte count, and elevation of alanine aminotransferase (ALT). Most of these side effects were mild and transient. The incidence of adverse events in the leflunomide group was 16.84%, significantly lower than that in MTX group (28.17%, P = 0.002). CONCLUSIONS: Leflunomide is effective in the treatment of RA with less adverse events than MTX. Its efficacy is similar to MTX, but the incidence of adverse events and the rate of withdrawal due to adverse events were lower in the leflunomide group than in MTX group.

Antirheumatic Agents↗

PubMed2002

Do NSAIDs affect the progression of osteoarthritis?

NSAIDs are widely used to alleviate the symptoms of OA. It remains controversial as to what effects these agents have on the progression of OA. In vitro studies showed several types of NSAIDs (e.g., sodium salicylate, indomethacin) inhibited the synthesis of cartilage matrix component, but some types of NSAIDs (e.g., aceclofenac, meloxicam, nimesulide) increased the matrix component synthesis and protected the chondrocytes against apoptosis, while others (e.g., piroxicam) had no effects. Studies in animal models verified that NSAIDs had favourable or detrimental action on OA progression, even the same NSAID (e.g., naproxen, tiaprofenic acid) had reverse effects on articular cartilage in different studies. Preliminary clinical trials revealed some NSAIDs such as indomethacin had a negative influence on joint structure, other NSAIDs such as diclofenac and naproxen had no acceleration of radiographic damage to OA within 2-years of treatment. So far, there are no convincing data to show the widely used NSAIDs and recommended selective COX-2 inhibitor have favourable effects on cartilage. Therefore, it is necessary and valuable to clarify the effects of these NSAIDs on cartilage in patients with OA using validated non-invasive methods such as MRI.

Animals↗

PubMed2002

Lumiracoxib (Novartis).

Lumiracoxib, an inhibitor of cyclooxygenase 2 (COX-2), is under development by Novartis for the potential treatment of osteoarthritis, rheumatoid arthritis and pain. By late December 2000, phase III trials had been initiated and were ongoing in December 2001.

Journal Article↗