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The effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on juxta-articular osteopenia and growth plate destruction adjacent to inflamed joints was investigated in rats with collagen-induced arthritis. Forty rats were assigned to the following six groups: (1) an untreated arthritis group; (2–5) arthritis rats receiving indomethacin (3 mg/kg per day), dexamethasone (0.2 mg/kg per day), or celecoxib (5 or 50 mg/kg per day), and (6) normal control rats. Drugs were administered for 2 weeks from the onset of arthritis. Then the hind paws were measured. Juxta-articular osteopenia and growth plate destruction adjacent to inflamed joints were also assessed using plain radiography, bone mineral density measurement, histology, and histomorphometry. Each treatment reduced inflammation, but only dexamethasone and high-dose celecoxib prevented bone loss adjacent to inflamed joints and significantly decreased bone resorption. In contrast, no treatment affected bone formation parameters. Growth plate destruction adjacent to inflamed joints was prevented by indomethacin, dexamethasone, and high-dose celecoxib. Although dexamethasone abolished inflammation, growth plate destruction was still observed. In conclusion, among the various drugs tested, only celecoxib had a preventive effect on both growth plate destruction and bone loss adjacent to inflamed joints in this arthritis model. [ABSTRACT FROM AUTHOR]

Macrophage colony-stimulating factor (M-CSF) is a key factor for osteoclastogenesis at the bone-pannus interface in patients with rheumatoid arthritis as well as a receptor activator of NF-kappaB ligand (RANKL). Imatinib mesylate inhibits the phosphorylation of c-fms, a receptor for M-CSF. The present study investigates the effect of imatinib mesylate on joint destruction in rats with collagen-induced arthritis (CIA) and on osteoclastogenesis in vitro. Imatinib mesylate (50 or 150 mg/kg), dexamethasone, or vehicle was administered daily to CIA rats for 4 weeks from the onset of arthritis. Hind-paw swelling and body weight were measured weekly. At weeks 2 and 4, the metatarsophalangeal (MTP) joints and the ankle and subtalar joints were radiographically and histologically assessed. The effect of imatinib mesylate on osteoclast formation from rat bone marrow cells with M-CSF and soluble RANKL (sRANKL) in vitro was also examined. Radiographic assessment showed that 150 mg/kg imatinib mesylate suppressed the destruction of the MTP and the ankle and subtalar joints at week 2, and MTP joint destruction at week 4 in CIA rats, although hind-paw swelling was not suppressed. The number of TRAP-positive cells at the bone-pannus interface was significantly reduced in the group administered with 150 mg/kg imatinib mesylate compared with that given vehicle at week 4. Imatinib mesylate dose-dependently inhibited the proliferation of M-CSF-dependent osteoclast precursor cells in vitro as well as osteoclast formation induced by M-CSF and sRANKL. These findings suggest that imatinib mesylate could prevent joint destruction in patients with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

The aim of this study was to elucidate the utility and limitation of gadopentetate (Gd)-enhanced MRI as a method for evaluating the anterior cruciate ligament (ACL) in the rheumatoid arthritis (RA) knee, using both surgical macro findings and histological findings to ascertain the pathological condition of the affected knee. Thirty-six knees of 25 RA patients were studied in this study. Four imaging protocols were employed: protocol A, T1-weighted and T2-weighted sagittal images; protocol B, T1-weighted sagittal image, after infusion of Gd-DTPA (0.2 mmol/kg, i.v.); protocol C, T1-weighted angled coronal image, parallel to the ACL; and protocol D, T1-weighted angled coronal image, parallel to the ACL, after infusion of Gd-DTPA. Sagittal image was determined as previously described. Angle coronal image was newly determined as coronal image parallel to the ACL. Surgical and MRI findings of the ACL were classified into four types: Type I (normal group) indicated that the thickness of the ACL was almost normal, adequate tension was maintained (surgical findings),and the ACL had thick and a more complex appearance with a homogeneous signal intensity and well-defined borders (MRI findings). Type II (degenerated group): the ACL had degenerated and tension was reduced (surgical findings), and the ACL had thin and a more complex appearance with a less homogeneous signal intensity and less well-defined borders. This appearance was more evident on Type II than Type I (MRI findings). Type III (ruptured group): the parenchyma of the ACL remained but lacked continuity (surgical findings), and the ACL appeared as partial lack of low signal intensity (MRI findings). Type IV (absent group): the parenchyma of the ACL was practically absent (surgical findings), and the ACL appeared as complete lack of signal low signal intensity (MRI findings). The concordance rate between surgical and MRI findings was investigated. Moreover, we investigated the extent to which histological changes of the ACL could be discriminated using MRI. In RA knees, the overall concordance rate between surgical and MRI findings was 41.7% under imaging protocol A. The overall rate improved up to 69.4% under imaging protocol B. But the overall rate dropped to 36.1% under imaging protocol C. The overall rate improved up to 83.3% under imaging protocol D. Especially, significant differences between imaging protocols A and B ( p<0.05), and imaging protocols C and D ( p<0.01), with respect to ACL degenerated group, were recognized. But significant differences between imaging protocols A and C, and imaging protocols B and D, with respect to ACL degenerated group, were not recognized. The concordance rate between histological and MRI findings was 41.7% in ACL normal group, and 61.5% in ACL degenerated group. The concordance rate between surgical and MRI findings was 100% in ACL normal group, and 78.9% in ACL degenerated group. There was a significant difference in the concordance rates between histological, surgical, and MRI findings in normal group ( p<0.05). The results of this study suggested that with Gd-enhanced MRI, the degree of synovial proliferation around the ACL and the degree of degradation of the ACL in the RA knee can be evaluated more accurately than with conventional MRI; however, in RA knees with severe synovial proliferation, it may be difficult to discriminate between the invasive synovium going into the ligament from synovium surrounding the ligament. This may be a limitation of Gd-enhanced MRI at present. In the clinical setting, the present imaging technique does allow the ligament to be evaluated to a certain degree, and may prove useful in the evaluation of temporal changes in the RA knee. [ABSTRACT FROM AUTHOR]

The purpose of this study was (1) to demonstrate a computer-assisted gait analysis system that can visualize the locus of the dynamic loading axis on the proximal tibia joint surface, and (2) to assess the accuracy of this system in a patient with bilateral knee osteoarthritis (OA). This system uses force plate data, CT skeletal structure data and motion capture data obtained from an infrared position sensor. The relative positions between bones and markers were used to calculate skeletal model movement based on movement of the markers. The locus of the dynamic loading axis on the knee joint was defined as the point on the proximal tibia joint surface that intersected with the loading axis of the lower limb, which passed through the centre of the femoral head and the centroid of multiple points surrounded by the distal tibia joint surface contour. To assess the accuracy of this system, open MRI was used to evaluate positions of skin markers against bones in six healthy volunteers. The locus in a patient was affected by differences between the varus knee with medial compartment OA on the non-operative side and the knee treated with high tibial osteotomy (HTO) on the opposite side. At knee flexion angles of 0°, 15° and 30°, the mean value of measurement error for point locations on the locus was within 5.6% of joint width in the lateral direction (JWLD) on the proximal tibia joint. This system can provide clinically useful information for evaluation of the dynamic loading axis on the knee joint surface. [Copyright &y& Elsevier]