Development of musculoskeletal toxicity without clear benefit after administration of PG-116800, a matrix metalloproteinase inhibitor, to patients with knee osteoarthritis: a randomized, 12-month, double-blind, placebo-controlled study.

We performed a randomized, double-blind, placebo-controlled, multicenter, parallel-group, dose-response study of the efficacy and safety of the oral administration of PG-116800, a matrix metalloproteinase (MMP) inhibitor, in patients with mild to moderate knee osteoarthritis. The primary efficacy endpoints included the progression of joint space narrowing in the osteoarthritic knee, as measured by microfocal radiography with fluoroscopic positioning, and the reduction of symptoms (pain and stiffness) and/or the improvement of function, as measured by the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). Four hundred and one patients were randomly assigned to either placebo (n = 80) or one of fourdoses of PG-116800: 25 mg (n = 81), 50 mg (n = 80), 100 mg (n = 80), or 200 mg (n = 80) taken twice daily for 12 months.

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.

Which radiographic techniques should we use for research and clinical practice?

Based upon published data, the different methods of imaging the knee joint are evaluated with respect to the radiographic procedure and anatomical structures recorded in: (1) images from radiographs of the tibiofemoral joint that have been obtained from the non-weight-bearing and weight-bearing extended knee views and the standardized knee flexion positions using fluoroscopy (semi-flexed and Lyon Schuss views) and non-fluoroscopic methods (MTP and fixed flexion); and (2) images from radiographs of the patellofemoral joint obtained from the lateral and the different axial views of the joint. Non-weight-bearing and weight-bearing radiographs of the knee in extension were found to be of limited value in assessing disease status, whereas all standing flexed knee positions reliably imaged joint space width and bone changes in the tibiofemoral joint. Fluoroscopic positioning of the joint is more demanding on equipment and personnel than non-fluoroscopic methods.

Relationships between tibial rim alignment and joint space width measurement reproducibility in non-fluoroscopic radiographs of osteoarthritic knees.

Rationale: Superimposition of the rims of the medial tibial plateau to within 1mm is an aim of fluoroscopic knee positioning protocols for osteoarthritic (OA) knee radiography and has also been proposed as a measure of quality for non-fluoroscopic methods.

Objective: To evaluate the effect of tibial rim alignment (TRA) on reproducibility of joint space width (JSW) measurement, both were measured from radiographs taken with each tibial plateau at a range of angles determined by different non-fluoroscopic views.

Methods: TRA and JSW measurements were taken from both knees of 100 OA patients each radiographed in fully extended, schuss/tunnel, and MTP views.

Reproducibility of the semiflexed (metatarsophalangeal) radiographic knee position and automated measurements of medial tibiofemoral joint space width in a multicenter clinical trial of knee osteoarthritis.

Objective: To determine the baseline and longitudinal consistency in reproducibility of the semiflexed metatarsophalangeal (MTP) position in repeat examinations of patients with knee osteoarthritis (OA) recruited for a multicenter clinical trial that terminated within one year (mean duration 0.81 yr), based on precise measurements both of minimum medial tibiofemoral compartment joint space width (JSW) and of tibial inter-rim distance.

Methods: Two technologists from 8 and one technologist from 14 clinical radiology units had received previous training in performing nonfluoroscopic semiflexed MTP knee examinations and in quality control criteria for film acceptance.

Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial.

Objective: To evaluate the safety and efficacy of long-term intraarticular (IA) steroid injections for knee pain related to osteoarthritis (OA).

Methods: In a randomized, double-blind trial, 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg (34 patients) or saline (34 patients) into the study knee every 3 months for up to 2 years. The primary outcome variable was radiologic progression of joint space narrowing of the injected knee after 2 years.

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.

Radiographic methods in knee osteoarthritis: a further comparison of semiflexed (MTP), schuss-tunnel, and weight-bearing anteroposterior views for joint space narrowing and osteophytes.

Objective: Current radiographic evaluation of knee osteoarthritis (OA) depends primarily on the presence and severity of joint space narrowing (JSN) and osteophytes. Radiographic JSN is a function of the actual JSN caused by articular cartilage loss and the observable JSN artifactually caused when the tibial and femoral surfaces diverge due to variations in patient's knee position. Views yielding the greatest JSN are the most accurate.