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.

Differences in trabecular structure between knees with and without osteoarthritis quantified by macro and standard radiography, respectively.

Objective: To compare the sensitivity of standard and macro-radiography for quantifying cancellous bone differences between subjects with and without medial compartment knee osteoarthritis (OA).

Methods: Patients with medial compartment knee OA (n=24) and non-OA reference subjects (n=10) had a standard and a macro-radiograph (x4 magnification) of one knee. Fractal Signature Analysis (FSA), a computerised image analysis technique, measured differences in cancellous bone structure between OA and non-OA tibiae in all radiographs.

Osteophytes, juxta-articular radiolucencies and cancellous bone changes in the proximal tibia of patients with knee osteoarthritis.

Objective: To determine differences in tibial cancellous bone organisation in knee osteoarthritis (OA) between the central weight-bearing region and juxta-articular radiolucencies adjacent to small, medium or large marginal osteophytes.

Methods: Patients with medial compartment OA (n = 60; F = 39), mean (SD) age 60.0 (9.

Review of the anatomical and radiological differences between fluoroscopic and non-fluoroscopic positioning of osteoarthritic knees.

Objective: To determine the differences in the radioanatomical appearance of the tibiofemoral compartment in knees radiographed in the fluoroscopic semiflexed, semiflexed MTP and fixed flexion methods compared to that obtained in the extended knee position. To assess the differences in the radiological procedures between the fluoroscopic and nonfluoroscopic semiflexed methods of radiography.

Methods: Based on anatomical principals to describe the differences in (1) the content of the joint space in knees radiographed in the extended and semiflexed positions and (2) the sectional plane for joint space width (JSW) measurement in radiographs of knees positioned in the extended, fluoroscopic guided semiflexed, MTP and fixed flexion positions.

Comparison of fixed flexion, fluoroscopic semi-flexed and MTP radiographic methods for obtaining the minimum medial joint space width of the knee in longitudinal osteoarthritis trials.

Objective: To compare three radiographic techniques (fluoroscopic semi-flexed [Fluoro], fixed flexion [FF], and semi-flexed metatarsophalangeal joint [MTP] views) for measuring medial joint space width (JSW) of the knee in longitudinal osteoarthritis (OA) trials and to identify the percentage of patients with detectable progression.

Design: Retrospective summary of the progression and variability of the change in JSW in knee OA.

Material And Methods: Data from the placebo arms of three separate, structure modifying, knee OA trials were compared including gender, age, baseline JSW, change from baseline in JSW, duration of observation, and number and percent of patients with joint space narrowing of various degrees.

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.

Cancellous bone changes in hip osteoarthritis: a short-term longitudinal study using fractal signature analysis.

Objective: To quantify changes to the trabecular structure in the femoral heads of patients with hip osteoarthritis (OA).

Methods: Patients with OA (n=14; F=7), mean (standard deviation age) 50.6 (10.

Tibial cancellous bone changes in patients with knee osteoarthritis. A short-term longitudinal study using Fractal Signature Analysis.

Objective: To quantify tibial cancellous bone changes over 24 months in patients with medial compartment knee osteoarthritis (OA) subdivided into those with slow or detectable joint space narrowing (JSN).

Method: Digitised macroradiographs (4x) were obtained at baseline and 24 months from 40 patients (F:26) and subdivided by computerised measurement of minimum medial compartment joint space width (JSW) into those with slow JSN (<0.2 mm/year, n=66) or detectable JSN (>or=0.

Cancellous bone differences between knees with early, definite and advanced joint space loss; a comparative quantitative macroradiographic study.

Objective: To quantify differences in bone structure in the proximal tibia of patients with mild, definite and advanced osteoarthritis (OA) compared to healthy reference tibiae.

Design: Patients with medial compartment OA (n=110; F=70), mean+/-SD age 61.0+/-10.

Subchondral bone changes in hand and knee osteoarthritis detected by radiography.

Objective: To describe the changes in subchondral bone that occur with the onset and progression of osteoarthritis (OA) from macroradiographic assessment of patient's hand and knee joints.

Design: The high magnification and spatial resolution of macroradiography permits detailed anatomical changes to be detected in OA joints. Data on the subchondral cortical and cancellous bone, recorded from both cross-sectional and longitudinal studies of hand and knee OA, are described and discussed with reference to recent findings on the altered biomechanical properties of OA bone.

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.

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.

Pattern of advancement in the zone of calcified cartilage detected in hand osteoarthritis.

Objective: Using high definition macroradiography the pattern of advancement in the zone of calcified cartilage (termed a ZCC step) was detected in osteoarthritic hand joints of patients and compared to the joint space width (JSW) measurement.

Design: X5 macroradiographs were obtained of the osteoarthritic hands of 44 patients at baseline and at 18 months. The incidence of ZCC steps, identified as an advancement in the mineralized cartilage front into articular cartilage, was assessed at each articular surface.

Advancement in the zone of calcified cartilage in osteoarthritic hands of patients detected by high definition macroradiography.

Objective: High definition macroradiography permits the advancement in the zone of calcified cartilage (described as a ZCC step) to be detected in osteoarthritic (OA) hand joints of patients. The pattern of their incidence and distribution was determined and compared to the joint space width (JSW) measurement.

Design: Macroradiographs, x5 magnification, were obtained of the OA hands of 44 patients at baseline and at 18 months.

Current status of imaging procedures in the diagnosis, prognosis and monitoring of osteoarthritis.

X-ray, magnetic resonance imaging (MRI) and arthroscopy are the methods most widely used to assess the status of osteoarthritic joints. How do these methods compare? As diagnostic tools, what is the relative sensitivity of X-ray versus MRI, arthroscopy versus MRI and arthroscopy versus X-ray? Which imaging modalities can be used for predicting progression? Scintigraphy and MRI can assess the degree of cellular activity in the tissues of a joint, which may help in prognosis. Are the methods proven and are they reliable? Recommendations for clinical trials in knee osteoarthritis, state it is essential that reproducible radiographs are obtained for reliable assessment of progression.

Protocols for precise radio-anatomical positioning of the tibiofemoral and patellofemoral compartments of the knee.

Quantitative assessment of radiographic features, in particular joint space width, are important in the diagnosis and treatment of knee osteoarthritis (OA). Protocols defining radiographic procedures are essential to maintain quality control and hence reliable and reproducible measurement of these features. Criteria governing variability in radiographic procedures are discussed and include defining the precise radio-anatomical position of the joint, standard criteria for X-ray beam alignment, allowance for inherent radiographic magnification and precise definition of anatomical boundaries.

Quantitative microfocal radiographic assessment of disease and progression in osteoarthritis of the hand.

Macroradiographic examination of the wrists and hands of 32 patients with osteoarthritis (OA) over an 18 month period showed that, compared with healthy control subjects, 44% of the patients had significant joint space narrowing at entry, which increased to 65%. Subchondral cortical thickness was greater in all patients at entry and increased with time. Osteophytes and juxtaarticular radiolucencies were present in all patients at study entry; by the end, osteophytes had increased in number and area, and juxtaarticular radiolucencies in area only.