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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. [ABSTRACT FROM AUTHOR]

Rationale: Minimum tibiofemoral joint space width in the medial compartment (JSW) is the most well-established structural outcome measure for osteoarthritis (OA) of the knee. Its usefulness as a measure of therapeutic effectiveness in short-term studies is limited by the rate and variability of joint space narrowing (JSN) in the OA population. Microfocal radiography has been shown to improve reproducibility of JSW measurement compared to standard radiography, but measurement of magnification from microfocal knee films has been problematic, and JSN is yet to be investigated in a longitudinal microfocal study., Objective: To establish the effect on JSW reproducibility of a new method of magnification measurement in microfocal radiographs. To report on and compare rates of medial tibiofemoral JSN and their variations in the placebo arms of microfocal and standard radiographic clinical trials in OA, using fluoroscopic semi-flexed (SF) knee positioning. To place in the context of published estimates of rates of JSN from comparable studies., Methods: Using microfocal radiography, 36 patients were followed at a single centre for 2 years. Using standard radiography, 86 patients were followed for 1 year at a single centre, and 549 for 2 years in a multi-centre international study. Computerised JSW measurement was undertaken using enhanced and automated versions of existing algorithms. Rates of JSN were examined in the context of a review of published rates of JSN using a variety of techniques., Results: Reproducibility of JSW measurement from microfocal radiographs was improved by the new magnification measurement. Rates of JSN were similar across the studies, but more variable when using standard radiography. The rates of JSN were also consistent with those from previously published investigations; all estimates since 2000, bar one, being consistent with the value 0.05 mm/year., Conclusion: Microfocal radiography using the new method lowered the variability of the rate of JSN, but the high cost and low availability of microfocal equipment remains a barrier to its more widespread use. The consistently low but highly variable rates of JSN seen in the review suggest that continued attempts to improve radiographic and mensural techniques are unlikely to significantly reduce required sample sizes.

Objectives: To determine whether risedronate (RIS) slows down trabecular bone loss in the medial compartment of the proximal tibia, a characteristic of patients with progressive knee osteoarthritis (OA)., Methods: Initially, 100 patients were randomly selected from each treatment group (each N approximately 300) comprising placebo and RIS 5 mg/day, 15 mg/day and 50 mg/week from a double blind, multi-centre, placebo-controlled, 2 yr investigation of OA knee patients in North America. Using fluoroscopic semi-flexed standard radiography, baseline and exit knee radiographs were digitized by laser scanner. Following computerized measurement of minimum medial compartment joint space width, each group was subdivided into joint space narrowing (JSN) non-progressor or JSN-progressor (JSN >or=0.6 mm measured at any point post-baseline). Computerized method of fractal signature analysis (FSA) quantified longitudinal changes separately in horizontal and vertical trabeculae in region of interest (three-fourth width of tibial compartment x 6 mm height) in the medial compartment. Following the initial study, all JSN-progressor knees within the entire patient cohort (N = 1232) were similarly analysed., Results: OA knees in JSN non-progressor group had a slight decrease in FSA for vertical and horizontal trabeculae and showed no drug effect. In JSN-progressor knees, bone loss was greater in both placebo and RIS 5 mg/day groups compared with those in RIS 15 mg/day group in which trabeculae were retained, and in the RIS 50 mg/week group in which the vertical trabecular number increased significantly (P < 0.05)., Conclusion: This preliminary study showed that patients with marked cartilage loss (JSN>or=0.6 mm) receiving RIS 15 mg/day retained vertical trabecular structure, and those receiving RIS 50 mg/week increased vertical trabecular number, thereby preserving the structural integrity of subchondral bone in knee OA.

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. Degree of TRA was compared with JSW reproducibility using correlation, and between groups defined both by the 1mm threshold and by TRA-defined quartiles., Results: JSW reproducibility was dependent on the degree of TRA in the fully extended and schuss/tunnel flexed knee views, although the use of the specific TRA threshold of 1mm was not supported. In the MTP view, JSW measurement was found to be highly reproducible across the full range of TRA values., Conclusion: These results contradict claims that TRA to within 1mm is essential for useful measurement of JSW. It is an arbitrary threshold, of use in quality control (QC) for protocols which explicitly require such alignment, and the choice of QC criteria for other protocols should be evaluated on a view-by-view basis. The results confirm previous studies showing the MTP view to afford highly reproducible JSW measurement.

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.

Objective: Fractal signature analysis (FSA), a computerized method of textural analysis, permits the separate measurement of changes in vertical and horizontal trabeculae based on the fractal dimension over a range of trabecular widths (fractal signature). We determined whether the FSA of high-definition macroradiographs (x5 magnification) quantified radiographic changes at sites of osteopenia and erosion formation in the rheumatoid arthritis (RA) hand., Methods: Sixty-seven RA patients had macroradiographs of the left wrist and hand. The distal radius was scored and grouped from very mild (RA1) to moderate (RA4) disease. Macroradiographs were digitized and FSA of horizontal and vertical trabecular organization was performed in the radius at sites of periarticular osteopenia, erosion formation and at a mid-metaphyseal site. The RA groups were compared with 11 healthy non-arthritic subjects using ANOVA and Dunnett's tests., Results: Compared to the non-arthritic hands, FSA at the distal radius in groups RA1 to RA4 measured significantly lower (P<0.05) fractal signatures. The fractal signatures were lowest in RA4 involving small, medium to large sized vertical trabeculae at the periarticular osteopenic (0.18 to 0.84 mm, P<0.01) and mid-metaphyseal sites (0.12 to 0.60 and 0.84 to 1.02 mm, P

Objective: In knee osteoarthritis (OA) damage to meniscal cartilage is associated with the changes in articular cartilage. Using double-contrast macroradiographs we determined whether the degree of meniscal cartilage damage was similar to or different from that at the corresponding regions of the articular cartilage on the tibia and femur., Design: Double-contrast microfocal macroradiographs,x7-x9 magnification, were obtained of the tibio-femoral joint in 20 osteoarthritic knee patients with medial compartment disease (Kellgren and Lawrence grades I-III). The appearance of the meniscus and the femoral and tibial articular cartilage were graded separately using a 5-point scale., Results: In the medial diseased compartment, articular cartilage damage on the tibia was similar to that of the meniscus, which had significantly greater (P<0.02) degenerative changes than the cartilage on the femur. In the lateral compartment, meniscal damage was significantly worse than in either tibial (P<0.04) or femoral articular cartilages (P<0.01), respectively; none was as severe as that in the medial osteoarthritic compartment., Conclusion: Although the cross-sectional nature of this study precluded definite aetiological inferences, this study showed that degenerative changes in the meniscal and articular cartilages were not totally variable. Because of its larger articular surface, changes in the medial femoral cartilage were less marked than at the meniscal and tibial cartilages in the osteoarthritic compartment. In the lateral compartment, meniscal damage precedes tibial and femoral articular cartilage changes. In knees with medial compartment OA, combined meniscal and articular cartilage damage would account for detection of radiographic joint space loss and not meniscal extrusion only.

Objective: To determine, in a preliminary cross sectional study of patients with anterior cruciate ligament (ACL) ruptured knees, which of the radiographic features-subchondral cortical plate thickness, trabecular sclerosis, and osteophytosis-appears before or in association with changes in joint space width (JSW) as a surrogate for articular cartilage thickness in patients with ruptured knees., Methods: 19 patients (14 men), mean (95% CI) age 28.7 (23.6 to 33.8) years, had ACL rupture in one knee only, confirmed by arthroscopy. Anterior draw, Lachman's test, and pivot shift tests were performed and x5 posteroanterior macroradiographs of both knees in a standing semiflexed view were taken at a mean (95% CI) time from injury of 34. 3 (26.9 to 41.7) months. In each radiograph, computerised methods were used to measure minimum JSW and fractal signature analysis (FSA) to quantify the vertical and horizontal trabecular organisation, osteophyte area, and the subchondral cortical plate thickness, in the medial and lateral tibial compartments of all knees., Results: Physical examination confirmed the presence of joint laxity in the injured knees. No statistical difference in either medial or lateral JSW and subchondral cortical plate thickness was detected between ACL ruptured and uninjured knees. FSA showed a significant decrease in fractal dimension for the horizontal trabeculae (size 0.42 mm) in the medial compartment of the ACL ruptured knees compared with the uninjured knees (p<0.01, multivariate analysis of variance). There was an inverse correlation (R -0.74) between the time since knee injury and the difference in FSA values for ACL ruptured and uninjured knees in medial compartment horizontal trabeculae (size 0.4 mm). No significant changes were detected in the lateral compartment. Osteophytes were detected in the medial compartment of nine ACL injured knees., Conclusion: Compared with the uninjured knee, ACL rupture leads to thickening of subchondral horizontal trabeculae (decreased FSA) in the medial tibial compartment of all knees, reaching significance at about four years after injury. Osteophytes were present in the same compartment in 9/19 knees. No changes in JSW and subchondral cortical plate thickness were detected. Whether the bony changes detected in these ACL ruptured knees presage those of early osteoarthritis requires further study.

Objective: The different radiographic procedures and methods for reading films and assessing the status and progression of hand osteoarthritis (OA) were reviewed., Methods: The methods that relate to each of the above procedures were assigned to categories upon which there was or was not general agreement., Results: It was agreed that the radiographic method should use published standardized radiographic protocols; that X-ray features should be graded separately for determining the extent of the disease and that changes in osteophyte size was the most sensitive indicator of progression. For epidemiological studies films should be read blind and randomly, but for assessing progression films should be read in pairs and in sequence. No agreement was obtained on the value of the lateral radiographic view of the hand nor on which radiographic atlas would be best for long-term longitudinal studies., Conclusions: Further work was required to evaluate the role of MRI and scintigraphy in hand OA; radiographic atlases could be improved by incorporating diagrams to illustrate the change in grade for each feature; validation was required for methods of assessment in long-term trials.

Microfocal radiography records, with unusually good resolution, the detailed structural organization of cancellous bone. A textural imaging method, fractal signature analysis (FSA), was used to quantify the horizontal and vertical trabecular organization recorded within macroradiographic images of the spine of post-menopausal women and the tibia in osteoarthritic knees, and the analysis of variance method was applied to the wrist and hand of rheumatoid patients. Changes in trabecular structure were found to correlate with (i) body weight, age and bone mineral density in the lumbar spine of post-menopausal women; (ii) the degree of cartilage loss and age in the tibia of patients with knee OA; and (iii) analysis of variance quantified the extent of 'normal', osteopaenic and eroded bone in rheumatoid joints. Quantitation of cancellous bone organization can add significantly to our understanding of disease processes and effect of therapy in diseased joints.

Objective: To determine whether fractal signature analysis (FSA) of digitised macroradiographs of knees quantifies alterations in trabecular structure in the tibial cancellous bone of osteoarthritic patients with either early or definite joint space narrowing compared with non-arthritic subjects., Methods: 90 osteoarthritic knees had macroradiographs at x5 magnification. Joint space width and FSA of horizontal and vertical trabecular organisation in the tibial subarticular cancellous bone were measured in the medial and lateral tibio-femoral compartments and compared to reference values obtained from the knees of 14 healthy non-arthritic volunteers, and to the subject's age and weight., Results: Compared to the non-arthritic joints, FSA of the trabecular structure of the medial diseased compartment of the tibia was significantly different and correlated with the degree of joint space narrowing (P < 0.003); FSA of horizontal trabecular structures decreased (P < 0.001) in knees with early osteoarthritis (joint space > 3 mm) and vertical trabecular FSA increased in knees with marked joint space narrowing (joint space < 3 mm). In the lateral compartment of the tibia, FSA did not show a difference between any of the categories. With increasing age of all subjects, the changes in FSA indicated a significant increase in the number of fine horizontal and vertical trabeculae. No correlation was found between the subjects' body weight and changes in the subarticular cancellous bone organisation., Conclusions: FSA quantifies changes in cancellous bone organisation in knee osteoarthritis. In the diseased compartment, increased horizontal trabecular thickness occurred early and preceded the later changes in the vertical structures.

Objectives: To improve the reproducibility and accuracy of joint space width (JSW) measurement as an assessment of cartilage loss in patients with osteoarthritis (OA) of the knee by determining how precision and accuracy of JSW measurement were altered by a computerised method of measurement, correction for radiographic magnification, radiography of the knee in the standing semiflexed view, and high definition macroradiography of the knee in the semiflexed view--taking JSW measurements from standard radiographs of OA knees in the extended view as the standard for comparison., Methods: Twenty five OA and 10 nonarthritic knees were radiographed in the extended view and minimum JSW was measured manually. Conventional and x5 macroradiographs were taken in the semiflexed view. All radiographs were taken twice on the same day and repeated two weeks later. Automated computerised measurement of minimum JSW was obtained from digitally stored images of all radiographs., Results: For medial compartment JSW measurements, computerised was more accurate than manual, correction for radiographic magnification improved precision and accuracy, measurements in the semiflexed view were more precise and accurate, and macroradiography increased measurement precision. For the lateral compartment JSW measurements, correction for radiographic magnification improved precision and accuracy, and the semiflexed view improved precision only., Conclusions: Protocols defining radiographic and mensural procedures are essential for quality control of knee radiography in the semiflexed view to permit accurate and reproducible measurement of JSW. Macroradiography provides greater precision of JSW measurement.

Objective: To test reliability of joint space width (JSW) measurements as a predictor of cartilage thickness in knees of patients with osteoarthritis (OA), using high definition microfocal radiography., Method: JSW was measured from weight bearing plain film macroradiographs taken in the tunnel view and compared with the sum of femoral and tibial cartilage thicknesses measured from double contrast macroarthrograms of the same regions of the same knees obtained in the non-weight bearing lateral position., Results: All knees had medial compartment OA. Comparison of the JSW with the sum of the tibial and femoral cartilage thicknesses revealed a highly significant correlation (p < 0.0001) between the two measurements in the medial but not the lateral compartment. In the middle region of both compartments, JSW was smaller than the cartilage thickness, indicating that, on standing, the curvature of the femoral condyles compressed the cartilage in this region., Conclusions: JSW reliably measured cartilage thickness in the medial but not the lateral compartment of knees with medial compartment OA. Depending upon the stage of OA disease, JSW reliably reflects cartilage thinning and compression.

Quantitative microfocal radiographic assessment of osteophytes in osteoarthritic hands showed that their number and area were greatest at joint margins, in the dominant hand, in the second and third compared with fourth and fifth phalanges, in the third phalanx, and in the second distal interphalangeal joint respectively. These sites correspond with those for the largest forces exerted in the hand: the dominant side, the finger tripod used in the precision grip, power grip, and pulp-pinch respectively. The greater osteophytosis on the trapezium of the nondominant first carpometacarpal joint was probably related to forces exerted during power grip. Osteophytes increased significantly in number and area during the 18 month study period.

Simultaneous clinical, scintigraphic, and macroradiographic assessments were carried out on 32 patients with hand osteoarthritis and the results at entry and one year reported. The presence and growth of osteophyte correlated with symptoms and a positive scan. The scan did not detect the radiographic features of juxta-articular radiolucencies, subchondral sclerosis, or cartilage thinning. Osteophytes, particularly when fast growing, produce pain, a 'hot' scan, and may predict disintegration of joint architecture.

We studied 32 patients with osteoarthritis who had 5x macroradiographs taken of their wrists and hands at 6-month intervals over an 18-month period. The higher magnification and resolution of microfocal radiography permitted the quantitative detection of progressive changes in 4 different features: subchondral sclerosis, the number and size of osteophytes, juxtaarticular radiolucencies, and joint space narrowing. Compared with normal control subjects, subchondral cortical thickness was greater in all patients at entry and showed a variable degree of change over the study period. Osteophytes and juxtaarticular radiolucencies were present in all patients at study entry; by the end of the study, osteophytes had increased in number and area, and juxtaarticular radiolucencies had increased in area, but not in number. At entry, 44% of the patients had joint space narrowing significantly greater than that in the control subjects; by 18 months, this proportion increased to 65%. No correlation was found between subchondral sclerosis, osteophytes, juxtaarticular radiolucencies, and joint space narrowing. We conclude that in osteoarthritis of the hand, the bony changes have progressed significantly before the occurrence of radiographically evident joint space narrowing indicative of cartilage thinning.

Quantitative macroradiographic examination of a group of early to moderately advanced rheumatoid patients showed the wrist and hand to have an average of 75 (SD 26) erosions out of 142 possible sites. Joint involvement was greatest in the wrist followed by the metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints respectively. In the wrist erosion distribution was concentrated in the radiocarpal and medial carpometacarpal complex, in the hand it tended to be located at the second and third MCP and third PIP joints. No difference was observed in erosion number and area between the right and left extremities. The distribution of the lesions is discussed in relation to the intra-articular pressures on normal hand function. The similarity of erosion development, across the joints at the different regions of the hand, suggests the presence of factors other than mechanical pressure. In general, erosions were widespread, and the largest erosions occurred in the larger bones of the wrist and hand.

The microfocal x-ray unit, a new type of x-ray machine characterised by an extremely small x-ray source, enables great detail to be recorded in the projection radiographs owing to the high object magnification and resolution obtained with this system. Microfocal radiographic examinations were carried out on the wrists and hands of 26 patients with early or moderately advanced rheumatoid arthritis. The macroradiographs confirmed the presence or absence of erosions in patients with early disease activity who otherwise had no detectable lesions visible in standard radiographs. The site of onset, development, and distribution of erosions are described. Their approximate order of appearance is listed. The first to appear occurred in the medial carpal bones, second and third metacarpophalangeal joints and third and fourth proximal interphalangeal joints. In origin they were subperiosteal either immediately adjacent to the insertion of an interosseous ligament or at the transitional zone of the articular cartilage. Erosions in the subchondral bone appeared subsequently and were either indirect (subperiosteal) or direct (subchondral) in origin. Cyst formation was frequently associated with the enlargement of an erosion which it often replaced.

Microfocal radiography, producing x5 magnified images of the wrist and hands with a high spacial resolution (25 microns) in the film, permitted direct measurement of erosion area and joint space width in patients with rheumatoid arthritis. The magnitude of errors relating to direct measurement, repositioning the wrist and hand on successive x ray visits, repeated identification of erosions and their area calculation were assessed. The coefficients of variation for length and area measurements were 3.7% and 13% respectively, while the change in joint space width and erosion area in five patients over 18 months had average coefficients of variation of 12.7% and 42.0% respectively. The combined errors correspond approximately to the fifth percentile level for the total changes in size of these x ray features. The remaining alterations were due to the disease, which was markedly greater that that attributable to errors of measurement.

Guinea-pigs were sensitized by intra-articular injection of M. tuberculosis (2.0 mg) into one knee joint and arthritis induced in the opposite knee 21 days later by intra-articular injection of antigen (0.2 mg). The time course off the arthritic changes was followed for 25 days by assessment of knee swelling and hind-limb flexion. Twenty-eight days after challenge the experiment was terminated and radiographic changes evaluated by means of a microfocal X-ray unit. The effect of treatment with the anti-rheumatic drugs, D-penicillamine (100 mg/kg by mouth), dexamethasone (0.1 mg/kg i.p.), aspirin (100 mg/kg by mouth), chloroquine phosphate (30 mg/kg by mouth) and sodium aurothiomalate (2 mg/kg i.m.) given daily from 10 days after sensitization until 28 days after challenge was assessed. Changes in joint swelling and hind-limb flexion were maximal 1-3 days after challenge. None of the drug treatments influenced these parameters. Microfocal radiography showed marked changes in arthritis animals of all X-ray parameters measured. It was possible readily to identify joint erosion, trabecular loss and associated osteoporosis, the latter occurring proximal to and relatively remote from the affected joint. None of the treatments prevented the radiographic changes but exacerbation of trabecular number in the area of the epiphysis was seen with aspirin and D-penicillamine and of trabecular density further up the shaft of the femur was seen with D-penicillamine. The changes with D-penicillamine may reflect the potentiation of cell-mediated hypersensitivity with this drug reported by other workers. It was concluded that the model is not suitable for the detection of clinically active anti-rheumatic drugs but that microfocal radiography provides a sensitive index for the assessment of joint damage in small animals.

Microfocal radiography has been used to evaluate the relation between erosion number and erosion area in the hands and wrists of 51 patients with early to moderately advanced rheumatoid arthritis. The hands of these patients showed different patterns of erosion progression, in terms of the relation between changes in number and area, and included those showing a decrease in one or both of the erosion parameters. The mean number of erosions in the group increased between the first and second visits. By the third visit (a mean of 48 months from the onset of symptoms) the mean number of erosions in the wrist and hand of the group had approached a constant value of 75 erosions. Over the same period the mean erosion area of the group continued to increase. Measurement of changes in erosion area is a more sensitive indicator of erosion progression than erosion number, both within the group and in individual patients.

The relatively low resolution in the radiographs produced by clinical X-ray machines has led to the rejection, by a number of investigators, of this machine as a method of examining the detailed structural organisation of bone. In the recently developed microfocal X-ray unit a fine beam of electrons is focussed onto the side of a water cooled target. Stereo-projection radiographs of specimens can be produced at magnifications of x 1-100 and a theoretical resolution to the diamter of the X-ray source (5-10 micrometer). The application of stereo-projection radiography to the study of cat skulls revealed details of structure not readily visible with conventional X-ray techniques. Using three different methods, the shadow images of trabeculae and vascular canals seen in the radiographs were closely correlated with the structures observed in the coronal sections and dissected regions of the cat skulls. The smallest structures recorded from the radiographs had a diameter of 60 micrometer. The effect of the depth of bone and of overlapping trabeculae and large vascular canals on the number of osseous structures recorded in the radiographs of five cat skulls was assessed. The results showed that 50% of the trabeculae and large vascular canals were no longer visible at a bone depth of 4 and 1x5 mm respectively and when superimposed by twelve and two structures respectively.