Biomedical subjects

Gary A Cline

Publications and source records attributed to Gary A Cline.

6 recordsLinked to original sources

PubMed2006

Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the two-year multinational knee osteoarthritis structural arthritis study.

OBJECTIVE: Bisphosphonates have slowed the progression of osteoarthritis (OA) in animal models and have decreased pain in states of high bone turnover. The Knee OA Structural Arthritis (KOSTAR) study, which is the largest study to date investigating a potential structure-modifying OA drug, tested the efficacy of risedronate in providing symptom relief and slowing disease progression in patients with knee OA. METHODS: The study group comprised 2,483 patients with medial compartment knee OA and 2-4 mm of joint space width (JSW), as determined using fluoroscopically positioned, semiflexed-view radiography. Patients were enrolled in 2 parallel 2-year studies in North America and the European Union. These studies evaluated the efficacy of risedronate at dosages of 5 mg/day, 15 mg/day, 35 mg/week (in Europe), and 50 mg/week (in North America) compared with placebo in reducing signs and symptoms, as measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and patient global assessment (PGA) scores, and in slowing radiographic progression. RESULTS: A reduction of approximately 20% in signs and symptoms, as measured by WOMAC subscales and PGA scores, was observed in all groups, with no treatment effect of risedronate demonstrated. Risedronate did not significantly reduce radiographic progression as measured by decreased JSW or using a dichotomous definition of progression (joint space loss of >or=0.6 mm). Thirteen percent of patients receiving placebo demonstrated significant disease progression over 2 years. A dose-dependent reduction in the level of C-terminal crosslinking telopeptide of type II collagen, a cartilage degradation marker associated with progressive OA, was seen in patients who received risedronate. No increase in the number of adverse events was demonstrated for risedronate compared with placebo. CONCLUSION: Although risedronate (compared with placebo) did not improve signs or symptoms of OA, nor did it alter progression of OA, a reduction in the level of a marker of cartilage degradation was observed. A sustained clinically relevant improvement in signs and symptoms was observed in all treatment and placebo groups.

Adult↗

PubMed2005

Long term evaluation of disease progression through the quantitative magnetic resonance imaging of symptomatic knee osteoarthritis patients: correlation with clinical symptoms and radiographic changes.

The objective of this study was to further explore the cartilage volume changes in knee osteoarthritis (OA) over time using quantitative magnetic resonance imaging (qMRI). These were correlated with demographic, clinical, and radiological data to better identify the disease risk features. We selected 107 patients from a large trial (n = 1,232) evaluating the effect of a bisphosphonate on OA knees. The MRI acquisitions of the knee were done at baseline, 12, and 24 months. Cartilage volume from the global, medial, and lateral compartments was quantified. The changes were contrasted with clinical data and other MRI anatomical features. Knee OA cartilage volume losses were statistically significant compared to baseline values: -3.7 +/- 3.0% for global cartilage and -5.5 +/- 4.3% for the medial compartment at 12 months, and -5.7 +/- 4.4% and -8.3 +/- 6.5%, respectively, at 24 months. Three different populations were identified according to cartilage volume loss: fast (n = 11; -13.2%), intermediate (n = 48; -7.2%), and slow (n = 48; -2.3%) progressors. The predictors of fast progressors were the presence of severe meniscal extrusion (p = 0.001), severe medial tear (p = 0.005), medial and/or lateral bone edema (p = 0.03), high body mass index (p < 0.05, fast versus slow), weight (p < 0.05, fast versus slow) and age (p < 0.05 fast versus slow). The loss of cartilage volume was also slightly associated with less knee pain. No association was found with other Western Ontario McMaster Osteoarthritis Index (WOMAC) scores, joint space width, or urine biomarker levels. Meniscal damage and bone edema are closely associated with more cartilage volume loss. These data confirm the significant advantage of qMRI for reliably measuring knee structural changes at as early as 12 months, and for identifying risk factors associated with OA progression.

Aged↗

PubMed2005

Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173].

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 >or= 25% or >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.

Adult↗

PubMed2005

Upper gastrointestinal tract safety of daily oral risedronate in patients taking NSAIDs: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the frequency of upper gastrointestinal (GI) tract adverse events associated with risedronate during two (2-year) randomized, double-blind, parallel-group, placebo-controlled studies. PATIENTS AND METHODS: Male and female patients aged 40 to 80 years with mild to moderate medial-compartment knee osteoarthritis were enrolled. Data were pooled and analyzed for risedronate at 5 mg and at 15 mg once daily and compared with placebo. The results of the once-weekly dosages (35 or 50 mg) were assessed separately. RESULTS: A total of 2483 patients were randomized: 622 to placebo, 628 to risedronate at 5 mg/d, 609 to risedronate at 15 mg/d, 310 to risedronate at 35 mg once weekly, and 314 to risedronate at 50 mg once weekly. During the study, 77% of patients were regular nonsteroidal anti-inflammatory drug (NSAID) and/or analgesic users (defined as those who took medication 23 days per week), and 68% were regular NSAID users. The number of upper GI tract adverse events was similar between treatment groups, with no dose-related response: 161 for placebo, 176 for rlsedronate at 5 mg/d, and 150 for risedronate at 15 mg/d. The time to the first upper GI tract adverse event was similar between treatment groups. There was no difference in the frequency of upper GI tract adverse events In risedronate-treated patients compared with patients who were regular users of NSAIDs or NSAIDs and/or analgesics. Findings were similar for those in the once-weekly risedronate groups. CONCLUSION: The results of this study show that risedronate regimens at 5 mg/d or 15 mg/d as well as once weekly at 35 mg or 50 mg are not associated with an increased frequency of upper GI tract adverse events, even in patients who have an increased risk for such events.

Adult↗

PubMed2004

Quantitative magnetic resonance imaging evaluation of knee osteoarthritis progression over two years and correlation with clinical symptoms and radiologic changes.

OBJECTIVE: To evaluate the change in osteoarthritic (OA) knee cartilage volume over a two-year period with the use of magnetic resonance imaging (MRI) and to correlate the MRI changes with radiologic changes. METHODS: Thirty-two patients with symptomatic knee OA underwent MRI of the knee at baseline and at 6, 12, 18, and 24 months. Loss of cartilage volumes were computed and contrasted with changes in clinical variables for OA and with standardized semiflexed knee radiographs at baseline at 1 and 2 years. RESULTS: Progression of cartilage loss at all followup points was statistically significant (P < 0.0001), with a mean +/- SD of 3.8 +/- 5.1% for global cartilage loss and 4.3 +/- 6.5% for medial compartment cartilage loss at 6 months, 3.6 +/- 5.1% and 4.2 +/- 7.5% at 12 months, and 6.1 +/- 7.2% and 7.6 +/- 8.6% at 24 months. Discriminant function analysis identified 2 groups of patients, those who progressed slowly (<2% of global cartilage loss; n = 21) and those who progressed rapidly (>15% of global cartilage loss; n = 11) over the 2 years of study. At baseline, there was a greater proportion of women (P = 0.001), a lower range of motion (P = 0.01), a greater circumference and higher level of pain (P = 0.05) and stiffness in the study knee, and a higher body mass index in the fast progressor group compared with the slow progressor group. No statistical correlation between loss of cartilage volume and radiographic changes was seen. CONCLUSION: Quantitative MRI can measure the progression of knee OA precisely and can help to identify patients with rapidly progressing disease. These findings indicate that MRI could be helpful in assessing the effects of treatment with structure-modifying agents in OA.

Arthrography↗

PubMed2003

X-ray technologists' reproducibility from automated measurements of the medial tibiofemoral joint space width in knee osteoarthritis for a multicenter, multinational clinical trial.

OBJECTIVE: To determine the reproducibility of x-ray technologists, 26 in North America (NA), 24 in Europe (EU), in reliably repositioning patient's osteoarthritic (OA) knees, from computerized measurements of minimum joint space width (JSW) and reproducibility in joint repositioning, during their training for the clinical trial. METHODS: Technologists from 12 NA and 12 EU clinical radiology units received identical training, at one site on each continent, in performing the fluoroscopically assisted semiflexed knee examination and in quality control criteria (QCC) for film acceptance. Subjects recruited were 129 in NA and 70 in EU, with both knees radiographed for some subjects. Each technologist radiographed 5 OA knees and repeated the process on the same knees 2 to 7 days later. Minimum medial JSW was measured at a single center on digitized images with computer software that corrected for radiographic magnification. Technologists' reproducibility in joint repositioning and JSW measurement was determined from the difference between test and retest. RESULTS: In all, only 3/50 technologists failed qualification criteria with a repeat-film JSW difference > 0.50 mm. The mean, standard deviation (SD) of the difference in JSW between test/retest for 146 NA film-pairs of -0.020 (0.16) mm was not statistically different from that in 120 EU film-pairs: -0.001 (0.18) mm. In NA and EU 45% of examinations achieved high quality, i.e., JSW difference between repeat films < 0.1 mm, and 92% achieved excellent to good quality with a difference between repeat films < 0.3 mm. NA and EU technologists' reproducibility was unaffected by subject's sex, age, and degree of JSW loss. Reproducibility in joint reposition for all technologists was excellent. CONCLUSION: Between-continent precision of JSW measurements from all accepted pairs of semiflexed views was excellent to very good and similar to the high technical quality achieved in the authors' original report. The value of training incorporating both test/retest radiographs and film QCC is essential for the high technical quality required for multinational clinical trials.

Adult↗