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

OsteoArthritis and Cartilage (2007) 15, 179e186 ª 2006 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.joca.2006.06.020

International Cartilage Repair Society

Osteophytes, juxta-articular radiolucencies and cancellous bone changes in the proximal tibia of patients with knee osteoarthritis E. A. Messent Ph.D., R. J. Ward Ph.D., C. J. Tonkin D.C.R.(R.) and C. Buckland-Wright D.Sc., Director* Department of Applied Clinical Anatomy, King’s College London, School of Biomedical Sciences, Guy’s Hospital Campus, London, UK Summary 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 ¼ 60; F ¼ 39), mean (SD) age 60.0 (9.7) years, and non-OA reference subjects (n ¼ 21; F ¼ 5), mean (SD) age 36.8 (11.5) years, had 4 macroradiographs digitised by laser scanner. Using a modified Osteoarthritis Research Society (OARS) Atlas, right and/or left knees were graded according to marginal osteophyte size into those with small (n ¼ 30), medium (n ¼ 30) or large (n ¼ 27) marginal osteophytes, identified as OPH1, OPH2 and OPH3, respectively. Non-OA knees (n ¼ 30) were anatomically normal. Computerised method of Fractal Signature Analysis (FSA) quantified differences in cancellous bone structure between non-OA and osteophyte subgroups at two regions of interest (ROIs); central weight-bearing and tibial margin. Results: Compared to non-OA, vertical trabecular number increased significantly (P < 0.05) in all osteophyte subgroups (width range 0.12e1.14 mm) within both ROIs. In OPH3, this increase was significantly (P < 0.05) greater compared to OPH2 in the central ROI, and to OPH2 and OPH1 in the marginal ROI at most trabecular widths (0.12e1.14 mm). In the marginal ROI, compared to non-OA, horizontal trabeculae number decreased in all osteophyte subgroups. This decrease was significantly greater in OPH3 compared to OPH2 and OPH1 at small to medium trabecular widths (0.12e0.54 mm). Conclusion: Compared to disease associated bone loss at the central ROI of the tibia, the extent of juxta-articular bone loss appears to be associated with the size of the marginal osteophytes. ª 2006 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Key words: Knee osteoarthritis, Osteophytes, Juxta-articular radiolucencies, Fractal analysis.

contribute to the pain reported in patients with radiographic osteophytes10,13. Osteophyte growth indicates metabolically active bone, with alterations not just confined to the region of bony growth14. Radiographic observation often reveals periarticular radiolucency adjacent to the osteophyte in knee OA (Fig. 1), indicating that the trabecular bone in this region is osteoporotic. Previously, localised osteoporosis has been reported beneath a thickened cortical plate in OA joints15e18. However, bone adjacent to the osteophytes has yet to be examined. This study will examine whether osteophyte size is associated with the extent of trabecular bone loss adjacent to the growing osteophyte, and whether this loss is comparable to that within the central weight-bearing region of the medial tibial compartment.

Introduction Active osteophyte growth is a hallmark of osteoarthritis (OA)1. It is this active bony growth at the joint margins that separates osteophytes that are characteristic of the disease from those that appear to be associated with ageing2. Marginal osteophytes are readily detected in radiographs and change in their size has been shown to be reliable and sensitive parameter for assessing disease progression3,4, therefore providing a method of grading OA severity5. Osteophytes develop following chondrocyte hypertrophy and endochondral ossification, a process that occurs in association with arterial proliferation6e8. Evidence of increased vascularity has been provided from bone scintigraphic studies that have revealed increased isotope uptake in joints with growing, active osteophytes9,10, including the actual site of osteophyte formation11. Further, angiogenesis is typically followed by innervation of new vessels by fine, unmyelinated sensory nerves12. This may

Patients and methods PATIENTS AND NON-OA REFERENCE GROUP

*Address correspondence and reprint requests to: Professor Christopher Buckland-Wright, D.Sc., Director, Department of Applied Clinical Anatomy, King’s College London, School of Biomedical Sciences, Hodgkin Building, Guy’s Campus, London Bridge, London SE1 1UL, UK. Tel: 44-20-7848-8036; Fax: 44-207848-8033; E-mail: [email protected] Received 6 March 2006; revision accepted 30 June 2006.

OA knees Following ethical committee approval obtained from the West Kent Health Authority and the Guy’s and St Thomas’ Hospital Trust, 60 patients (39 female), mean (SD) age 60.0 (9.7) years; mean (SD) body mass index (BMI) 28.8 179

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E. A. Messent et al.: Changes in the proximal tibia of patients with knee OA joint, thus permitting determination of radiographic magnification within the plane of the joint. All macroradiographs were digitised using the high resolution Lumysis 200HR laser film digitiser (Lumysis, Sunny Vale, CA) at a pixel resolution of 60 mm by 60 mm (after correction for magnification) and the images were stored and analysed (Sun Sparcstation, model 20/61, Sun Microsystems Ltd). Image analysis software developed in our department called Mdisplay23 was used to calculate fractal signature of ROIs within the images. GROUPING OF OA KNEES ACCORDING TO OSTEOPHYTE SIZE

Fig. 1. Macroradiograph (4 magnification) of a right knee with medial compartment OA. Periarticular osteopenia is present within subchondral bone adjacent to the osteophyte growing at the margin of the medial compartment. Reproduced at 3.9 magnification.

(4.6) kg/m2 with early, definite and advanced radiographic medial compartment knee OA were recruited from those attending the hospital based Rheumatology clinics, as well as patients obtained directly from General Practices. All patients were diagnosed according to the standard criteria for knee OA19, and had pain in one or both knees for at least 1 month. These were carefully examined clinically to exclude other types of arthritis, evidence of trauma, previous surgical intervention, or treatment with corticosteroids. Prior to the study, drug therapy was not controlled and therapeutic agents included Non-Steroidal Anti-Inflammatroy Drugs (NSAIDs) and use of analgesics. Baseline macroradiographs of both knees from each patient were prepared. Knees with evidence of marginal osteophyte formation within the medial tibial compartment were selected for analysis, giving 87 knees in total.

Non-OA knees As ethics considerations precluded taking X-rays of non-diseased age and sex matched subjects, 21 healthy, non-arthritic volunteers were recruited from medical and laboratory staff. Sixteen men and five women had a mean (SD) age of 36.8 (11.5) years and a mean (SD) BMI of 26.0 (3.5) kg/m2. Macroradiographs of both knees were obtained from male and female subjects and selection was based upon availability, giving 30 knees in total. MACRORADIOGRAPHS AND DIGITISATION OF MACRORADIOGRAPHS

High definition posteroanterior macroradiographs20,21 of the knees were obtained at magnifications between 3.5 and 5 in the standing semiflexed view22. The centre of the joint, defined by the joint space, was aligned with the centre of the X-ray beam with the aid of a cross-optic laser. Using fluoroscopy, each knee was flexed until the tibial articular surface was horizontal relative to the floor, parallel to the central X-ray beam and perpendicular to the X-ray film. Radiographic magnification was determined from automated measurement of the diameter of a metal ball which was taped to the skin over the tibial tuberosity. Lateral films of the knee were obtained at the same time in order to determine the distance from the metal ball to the centre of the

OA knee macroradiographs were sub-grouped into those with small, medium or large marginal osteophytes within the medial tibial compartment. Most patients within our cohort had early symptoms of OA, therefore modification of the standard Osteoarthritis Research Society (OARS) radiographic Atlas5 was necessary in order to account for the more limited range of osteophyte sizes present. Knees with osteophytes smaller than OARS grade 1 were identified in our study as group OPH1 [Fig. 2(a)]. Knees with osteophytes greater than OARS grade 1 but smaller than OARS grade 2 were identified as group OPH2 [Fig. 2(b)]. Knees with osteophytes equivalent to OARS grade 2 or 3 were identified as group OPH3 [Fig. 2(c)]. Using weighted Kappa statistics24, intra-observer agreement was 0.87 and inter-observer agreement was 0.66, described as ‘very good’ and ‘good’ agreement, respectively24. Demographic data for all groups are presented in Table I. REGIONS OF INTEREST

Two separate ROIs were identified for the assessment of subchondral trabecular bone structure within the medial tibial compartment: (1) at the central weight-bearing region [identified as (C) in Fig. 3] and (2) at the tibial margin [identified as (M) in Fig. 3]. The height and width of each ROI measured 100 pixels (6 mm). The upper border of the central ROI was located in the centre of the medial tibial compartment subjacent to the cortical plate, drawn onto the image by an automated ridge-tracing function in Mdisplay (Fig. 3). The upper border of the ROI at the tibial margin was located subjacent to cortical plate, and the lateral border was located just within the margin of the tibial shaft (Fig. 3). MEASUREMENT OF SUBCHONDRAL AND SUBARTICULAR CANCELLOUS BONE

Fractal analysis is a robust method25,26 which is independent of a range of factors that may vary during routine radiographic procedure, such as the effect of radiographic magnification and projection geometry25e27, changes in object or patient positioning25e30 and variations in the sensitometric properties of radiographs such as film contrast and mean density25e30. Studies have shown that fractal dimension (FD) of trabecular bone obtained from projection images is related to three-dimensional microarchitecture31e33 and that the ageing process leads to an increase in FD of mostly small sized vertical structures (0.30 mm)34. Fractal Signature Analysis (FSA), a technique developed within our unit25, computed FD separately for vertical and horizontal trabecular structures ranging from 0.12 mm to 1.14 mm in increments of 1 pixel (0.06 mm) for each ROI. This range of widths was chosen because trabecular thicknesses in the proximal tibia have been shown

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Fig. 2. Teaching macroradiographs (4 magnification) for groups (a) OPH1 (marginal osteophyte equivalent to OARS grade >0, <1); (b) OPH2 (marginal osteophyte equivalent to OARS grade >1, <2); and (c) OPH3 (marginal osteophyte equivalent to OARS grade 2, 3). Arrow indicates osteophyte. Diameter of ball bearing ¼ 5 mm.

to fall within this range35,36. The coefficient of variation for testeretest for FSA measurements has been previously calculated as 2.1%37.

the non-arthritic reference group (Fig. 4). Each graph presented the differences in fractal signature for the range of trabecular widths from 0.12 mm to 1.14 mm. Data points below the abscissa corresponded to a decrease in complexity

STATISTICAL ANALYSIS AND PRESENTATION OF DATA

Differences in the vertical and horizontal trabecular structures between the non-arthritic reference group and each osteophyte subgroup were determined using the unpaired t test. To simplify graphical presentation, the mean fractal signature for each OA group was subtracted from that of Table I Demographic data of non-OA reference group and osteophyte subgroups; small (OPH1), medium (OPH2) and large (OPH3) marginal osteophytes in the medial tibial compartment Group

N Equivalent Age, (SD) Weight, (female) OARS Atlas years (SD) Kg Grade

BMI, (SD) kg/m2

Non-OA 30 (10)

0

38.6 (11.4) 81.6 (10.2) 26.0 (3.4)

OA knee subgroups OA1 30 (19) OA2 30 (18) OA3 27 (18)

>0 <1 1 <2 2 or 3

55.1 (9.8) 78.9 (16.6) 28.7 (4.1) 59.8 (10.3) 81.2 (14.1) 28.7 (5.4) 65.5 (7.0) 85.1 (8.0) 31.3 (4.5)

Fig. 3. Macroradiograph (4 magnification) of a proximal right tibia showing placement of the central weight-bearing (C) and marginal (M) ROIs. Broken line indicates the inferior margin of the cortical plate. Reproduced at 3.9 magnification.

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0.35 0.25

(b) i)

0.15 0.05 -0.05 0

0.24

0.48

0.72

0.96

1.2

-0.15

Difference in Fractal Dimension

Difference in Fractal Dimension

(a)

0.35 0.25

i)

0.15 0.05 -0.05 0

0.24

0.35

ii)

0.05 0.24

0.48

0.72

0.96

1.2

-0.15

Difference in Fractal Dimension

Difference in Fractal Dimension

1.2

Vertical trabecular width, mm

0.15

-0.05 0

0.96

-0.15

Vertical trabecular width, mm

0.25

0.72

-0.25

-0.25

0.35

0.48

0.25

ii)

0.15 0.05 -0.05 0

0.24

0.48

0.72

0.96

1.2

-0.15 -0.25

-0.25

Horizontal trabecular width, mm

Horizontal trabecular width, mm

Fig. 4. The mean difference in FD for vertical (i) and horizontal (ii) trabecular structures between OA groups (OA1 , OA2 , and OA3 ) and the non-OA group (NOA) in the central weight-bearing (a) and marginal (b) regions of interest. Significant differences indicated at P < 0.05 -, P < 0.01 -, and P < 0.001 ,.

of the image texture (reduction in the FD), associated with a decrease in trabecular number, whereas those above the abscissa corresponded to an increase in complexity (increase in the FD), associated with an increase in trabecular number resulting from thinning and fenestration of coarser trabeculae. The significance level for both statistical tests was set at P < 0.05, with P < 0.01 and P < 0.001 identified wherever appropriate. For purposes of discussion, trabeculae were referred to as those that were small (width range: 0.12e0.42 mm), medium (width range: 0.48e0.78 mm), and large (width range: 0.84e1.14 mm). Significant differences between osteophyte groups were determined using one-way analysis of variance (ANOVA) followed by the post hoc Tukey test for multiple comparisons. Statistically significant fractal signature differences were similarly determined at P < 0.05 for each trabecular width measured, with P < 0.01 and P < 0.001 identified wherever appropriate.

Results CENTRAL WEIGHT-BEARING REGION

[Fig. 4a(ii)]. Differences between OPH groups were minimal [Table II(b)]. MARGINAL ROI NEXT TO OSTEOPHYTE

Vertical trabecular structures Compared to the reference group, vertical trabecular number increased significantly (P < 0.05) in all OPH groups [Fig. 4b(i)] at a range of trabecular widths (0.12 mm to 1.14 mm) due to thinning and fenestration. This increase was significantly greater (P < 0.05) in OPH3 compared to OPH1 and OPH2 at most trabecular widths (0.12 mm to 1.14 mm) [Table II(a)].

Horizontal trabecular structures Compared to the reference group, horizontal trabecular number decreased in all OPH groups [Fig. 4b(ii)] due to decrease in trabecular number. This decease was significantly greater (P < 0.05) in OPH3 compared to OPH1 and OPH2 at small to medium trabecular widths (0.12 mm to 0.54 mm) [Table II(b)].

Vertical trabecular structures Compared to the reference group, vertical trabecular number increased significantly (P < 0.05) in the OPH3 group at all trabecular widths (0.12 mm to 1.14 mm) and in the OPH1 and OPH2 groups at small to medium trabecular widths (0.36 mm) [Fig. 4a(i)] due to thinning and fenestration. This increase was significantly greater (P < 0.05) in OPH3 compared to OPH2 at most trabecular widths (0.12 mm to 1.14 mm) and to OPH1 at a single width (0.12 mm) [Table II(a)].

Horizontal trabecular structures Compared to the reference group, apart from the smallest trabecular widths (0.18 mm), there were no significant differences in horizontal trabecular number in any OPH group

Discussion Our results have confirmed that the degree of thinning of vertical trabeculae and loss of horizontal trabeculae within bone adjacent to the marginal osteophyte are related to osteophyte size (Fig. 4). The differences in bone structure occurred at small, medium and large vertical and horizontal trabecular widths, demonstrating that these differences were disease-related rather than due to the greater mean age of the OA group, as previous studies have shown that the ageing process produces thinning of predominantly small vertical trabeculae (0.30 mm) 34. Further, there were substantial differences in bone structure across the medial compartment. This was shown by a greater degree of vertical trabecular thinning and loss of horizontal trabeculae

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Osteoarthritis and Cartilage Vol. 15, No. 2 Table II Mean differences in vertical (a) and horizontal (b) Fractal Dimension between osteophyte groups OPH1, OPH2 and OPH3 in the Central ROI and Marginal ROI Trabecular width (mm)

Mean difference in Fractal Dimension Central ROI

Marginal ROI

OPH3e OPH3e OPH2e OPH3e OPH3e OPH2e OPH2 OPH1 OPH1 OPH2 OPH1 OPH1 (a) Vertical trabeculae 0.12 0.06 0.11z 0.05 0.18 0.06* 0.05 0.01 0.24 0.07* 0.03 0.04 0.30 0.07 0.03 0.04 0.36 0.06 0.04 0.02 0.42 0.07 0.05 0.01 0.48 0.09* 0.07 0.01 0.54 0.11* 0.09 0.02 0.60 0.14y 0.09 0.05 0.66 0.15* 0.08 0.07 0.72 0.15* 0.07 0.08 0.78 0.12 0.08 0.03 0.84 0.10 0.09 0.01 0.90 0.15* 0.11 0.05 0.96 0.19* 0.10 0.09 1.02 0.20y 0.09 0.11 1.08 0.21y 0.08 0.14 1.14 0.22y 0.10 0.13 (b) Horizontal trabeculae 0.12 0.08* 0.14z 0.18 0.03 0.03 0.24 0.01 0.03 0.30 0.03 0.06 0.36 0.04 0.06 0.03 0.05 0.42 0.48 0.02 0.06 0.54 0.00 0.05 0.60 0.03 0.01 0.66 0.06 0.04 0.72 0.11* 0.08 0.78 0.16 0.12 0.84 0.11 0.09 0.90 0.02 0.01 0.96 0.01 0.02 1.02 0.01 0.02 1.08 0.01 0.03 1.14 0.01 0.02

0.06* 0.00 0.02 0.02 0.02 0.02 0.04 0.05 0.04 0.02 0.03 0.04 0.03 0.01 0.00 0.02 0.02 0.01

0.06 0.06 0.10* 0.13 0.14* 0.15y 0.16y 0.17y 0.18y 0.17y 0.16y 0.15y 0.17y 0.20z 0.21z 0.22z 0.23z 0.23z

0.09y 0.04 0.08 0.12* 0.17y 0.21z 0.23z 0.26z 0.26z 0.26z 0.26z 0.24z 0.25z 0.28z 0.27z 0.28z 0.30z 0.28z

0.03 0.02 0.02 0.01 0.03 0.06 0.07 0.09 0.09 0.09 0.10 0.09 0.08 0.08 0.07 0.06 0.07 0.05

0.03 0.05 0.10y 0.13z 0.15z 0.16z 0.15y 0.11* 0.09 0.10 0.08 0.09 0.10 0.10 0.08 0.07 0.05 0.02

0.08y 0.05 0.13z 0.16z 0.18z 0.18z 0.17z 0.14y 0.10 0.10 0.09 0.09 0.08 0.10 0.10 0.10 0.08 0.04

0.04 0.00 0.02 0.03 0.03 0.02 0.03 0.03 0.01 0.01 0.00 0.00 0.01 0.00 0.02 0.03 0.03 0.02

Significance levels: *P < 0.05; yP < 0.01; zP < 0.001.

adjacent to the marginal osteophyte compared to the thinning of vertical trabeculae only in the central region of the tibial plateau [Fig. 4a(i) and b(i)]. CENTRAL WEIGHT-BEARING ROI

Compared to the reference group, the principle finding within the central ROI of all osteophyte subgroups was increased FSA of vertical trabeculae, consistent with increased vertical trabecular number associated with thinning and fenestration of coarser trabeculae38e40 (Fig. 5). Localised osteoporosis in the subchondral bone is attributed to early disease-related changes occurring subsequent to cortical plate thickening41, detected in other studies as a significant decrease in bone mineral density17,18. Thinning of trabeculae and demineralisation beneath a thickened subchondral cortical plate have been reported in both animal models of OA42 and OA patients17,43.

This cortical plate thickening, combined with flattening and increased congruity between the articular surfaces41,44,45, could cause osteopaenia in the subarticular bone due to decreased load transmission in a similar way to ‘stress shielding’ observed in bone under metal prostheses46,47. The subchondral thinning and fenestration of vertical trabeculae increased for each subgroup from small through to large osteophytes. This finding was similar to that observed in our previous study of the central weight-bearing region in which patients were grouped according to the degree of medial compartment joint space narrowing15. These results confirm the association between osteophyte growth and cartilage destruction48,49. However, the extent of vertical trabecular thinning and fenestration in knees with early to moderate joint space narrowing was greater than that found in knees with small to medium osteophytes15. This suggests the process of bony changes associated with the disease process, including osteophytosis and subchondral trabecular remodelling, is already well established by the time cartilage damage is quantifiable radiographically as joint space narrowing. This observation has been supported by previous longitudinal studies of OA in which osteophyte growth occurred prior to50, or in the presence of, minimal51 joint space narrowing. Although the processes involved in joint destruction are complex, it is likely that this early remodelling of subchondral bone, resulting in alteration to its biomechanical52,53 and structural composition41,44,45, may not only be associated with the initiation of cartilage damage53, but also osteophyte formation. Indeed, recent work has suggested that chemical agents released by damaged chondrocytes more centrally within the articular cartilage permeate through the cartilage matrix to the ‘cartilage synovium’ at the outer tibial margin, leading to differentiation of mesenchymal tissue in this area54. The resultant cartilaginous tissue is then invaded by blood vessels probably from the periosteum, establishing the process of endochondral ossification and growth of an osteophyte54 (Fig. 6). MARGINAL ROI NEXT TO THE OSTEOPHYTE

Compared to the central region of the tibial plateau, the degree of vertical trabecular thinning within the subchondral bone next to the marginal osteophyte was greater in all osteophyte subgroups, as detected by marked increase in FSA [Fig. 4a(i) and b(i)]. Further, marked loss of horizontal trabeculae occurred next to large osteophytes [Fig. 4b(ii)]. This shows that the degree of trabecular remodelling is highly localised within the medial compartment and different between the central and marginal ROIs. Whereas thickening of the subchondral cortical plate may contribute to localised thinning and loss of bone within the central weight-bearing region of the compartment41, synovial inflammation and related changes to the vascular environment may be linked to the substantial thinning of subchondral trabeculae in the region next to the tibial margin. Chronic synovitis has been reported in OA joints including the hip55, hand56 and knee57 and may occur in up to one-third of patients undergoing total joint replacement58. Studies of hand OA have reported that juxta-articular radiolucencies are detectable on radiographs4. Although these radiolucencies are smaller than rheumatoid erosions58, their similarity and site of occurrence58,59 support the clinical evidence for the role of an inflammatory process in OA57,60. Juxta-articular radiolucencies identify areas of degraded

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Fig. 5. Macerated preparations of lumbar vertebrae from subjects with ‘normal’ structure (a) and mild osteoporosis (b)38. The higher FSA values for vertical trabeculae (b) are due to the increase in number of cross-connectivity of fine trabecular structures.

bone that has undergone thinning and loss of trabeculae. Our results confirmed that both these processes had occurred. The progressive increase in FSA of vertical trabeculae corresponded to thinning and fenestration of vertical trabeculae [Fig. 4b(i)]38. The progressive decrease in FSA of horizontal trabeculae corresponded to a decrease in the number of horizontal structures detected [Fig. 4b(ii)]16. The association between decrease in FSA and vertical and horizontal trabecular loss has been confirmed in a separate study examining trabecular bone at erosion sites in joints with inflammatory arthritis61. The authors reported a progressive decrease in FSA as the erosion site became more radiolucent61. In OA tibiae, horizontal trabeculae may be removed in preference to vertical trabeculae due to the greater importance of the latter in load-bearing in the knee joint. Preliminary work, based upon radiographic observation and patient symptomology, supports a link between chronic synovitis and radiolucencies at the joint margin. In hand OA, there is a strong association between fast growing

Meniscus Cartilage

Cartilage synovium Cartilage bud with vascular invasion from the periosteum

osteophytes and pain10, and pain is linked to an inflamed synovium57. Further work needs to be undertaken in order to determine the relationship between the extent of synovial inflammation and its association with osteophyte formation. Recent work has shown that vascular invasion of the articular cartilage, probably from the periosteum, initiates the process of endochondral ossification leading to osteophyte development54. The vascular supply of the osteophyte is therefore completely separate from that of the adjoining subchondral bone54 (Fig. 6). This may explain how bone formation at the osteophyte site can occur in close proximity to trabecular thinning and loss within the juxta-articular radiolucency next to the osteophyte. SUMMARY

Compared to healthy reference knees, trabecular bone within the central region of the medial tibial compartment was thinner and more fenestrated, and the degree of thinning of vertical trabeculae increased in conjunction with increasing marginal osteophyte size. This, it is suggested, is due to progressive thickening and flattening of the subchondral cortical plate41,44,45 which may produce a ‘stress shielding’ effect, resulting in thinning and loss of trabeculae in the subchondral bone. Progressive thinning of vertical trabeculae and loss of horizontal trabeculae also occurred in bone adjacent to growing osteophytes, resulting in a greater degree of localised osteopenia compared to the central region of the compartment. This may be linked to the chronic inflammation reported within the synovium of many osteoarthritic joints56,59,60,62, leading to ‘juxta-articular radiolucencies’ similar to those seen in patients with inflammatory arthritis49e51.

Capsular synovium Periosteal blood vessels Capsule

Fig. 6. Schematic diagram showing the development of a tibial marginal osteophyte, with blood vessels from the periosteum invading the cartilage bud. Modified after Alonge et al.54.

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