The Achilles tendon insertion is associated with a complex of adjacent fibrocartilages, a bursa, and a fat-pad, and is functionally much more than a focal insertion. This has important implications for a better understanding of the spondylarthropathies (SpA). However, the degree to which other insertions form comparable “enthesis organs” has not been established. The aim of this study was to demonstrate the applicability of the enthesis organ concept to other insertion sites.
Both joint-related (articular) and extraarticular entheses were removed from 28 sites in the limbs of formalin-fixed cadavers (age at death 70–101 years) that had been donated for anatomic study. The samples were prepared for paraffin histologic analysis and sectioned longitudinally. The presence and extent of enthesis organs was evaluated at each site in serial sections stained with Masson's trichrome and toluidine blue.
Articular enthesis organs were found at 14 entheses, including the attachments of the digital extensor tendons and collateral ligaments, the cruciate ligaments, tibialis anterior, the lateral collateral ligament of the knee, and the popliteal tendon. Extraarticular enthesis organs were seen at 2 sites, the biceps brachii and patellar tendon insertions. In all enthesis organs, sesamoid and/or periosteal fibrocartilage was present in close association with synovium.
The concept of an enthesis organ is of general significance in understanding attachment sites and may explain the diverse pathologic changes, including synovitis, bursitis, and extracapsular changes, seen adjacent to tendon/ligament entheses in SpA. These findings may provide insight into the reason the target tissues in SpA are apparently so diverse.
The enthesis is the region in which a tendon, ligament, or joint capsule attaches to bone, and much of the pathology in the spondylarthropathies (SpA) can be directly attributed to disease at that site. Although enthesopathies are traditionally viewed as focal, insertional disorders, findings on magnetic resonance and ultrasound imaging suggest the presence of more diffuse changes with involvement of the adjacent bone and soft tissue. Thus, in SpA, inflammatory changes may occur some distance from the insertion site (1–4), and lateral epicondylitis is linked to degenerative changes not only at the entheses associated with the common extensor origin, but also in adjacent ligaments (5–8). We believe such findings are best understood by viewing insertion sites not merely as focal attachments, but as parts of an “enthesis organ complex” that may dissipate stress concentration at the bony interface away from the attachment site itself (9).
The archetypal enthesis organ is that of the Achilles tendon, which Canoso has aptly described as having the “première enthesis” (10). Here, stress is dissipated away from the osteotendinous junction by contact between the adjacent parts of the tendon and bone in a dorsiflexed foot (9–11). The enthesis organ comprises not only the enthesis itself, but also fibrocartilages in the walls of the adjacent retrocalcaneal bursa, together with the bursal cavity and its associated synovium-covered fat-pad (9, 11). The fibrocartilages include a sesamoid fibrocartilage in the deep part of the tendon and a periosteal fibrocartilage on the opposing superior tuberosity of the calcaneus. They replace the synovial membrane that lines the bursa more proximally, and it would be difficult to envisage disease of these structures in SpA without adjacent synovitis, since they are so intimately linked (9).
While the “enthesis organ” concept is clearly relevant for understanding Achilles insertional tendinopathies, the extent to which it applies to other attachment sites is less clear. From a clinical perspective, the changes in SpA may include synovitis, bursitis, and diffuse, fusiform, synovial joint swelling. Such changes attest to the fact that the enthesis-related pathology is more than insertion-point inflammation. The purpose of this study was to determine the general applicability of the enthesis organ concept, by evaluating a wide range of entheses including those within joints, adjacent to joints, and at extraarticular sites. We demonstrated that insertions at many sites frequently form part of enthesis organs that are intimately associated with a synovial cavity and thus with synovial membrane. These findings may be central to elucidation of the relationship between enthesitis and synovitis and for recognition of the diverse clinical presentations of SpA. They thus have implications with regard to a better understanding of the disease mechanisms.
MATERIALS AND METHODS
A wide range of entheses from 28 different sites were obtained from the upper and lower limbs of cadavers (both sexes; age at death 70–101 years) at the University of Cardiff and the University of Innsbruck. The cadavers had been donated for anatomic study (medical histories were not available) and had been perfused with a solution containing formaldehyde and alcohol; details have been reported previously (11). Between 2 and 11 specimens were examined for each enthesis. The attachment sites chosen are listed in Table 1. The rationale for the selection of sites was 1) the inclusion of “articular” entheses that attached within a synovial joint (e.g., the cruciate ligaments [which are entirely intraarticular, yet extrasynovial] and the popliteal tendon/lateral collateral ligament complex) or replaced part of the joint capsule (e.g., digital extensor tendons, interphalangeal joint collateral ligaments, and the insertional tendons of tibialis anterior and fibularis brevis) and were thus intimately juxtaposed with its synovium, 2) the inclusion of extraarticular entheses that were close to joints and associated with subtendinous bursae (e.g., the pes anserinus and biceps brachii insertional tendons), and 3) the inclusion of entheses from regions in which periostitis occurs.
Forms a complex enthesis organ; SF sometimes present in deep surface; articular cartilage acts as a PF; closely related to synovium
Anterior cruciate ligament (tibial attachment)
The tibial spine is covered with articular cartilage, which acts as a PF; No SF; closely related to synovium
Anterior cruciate ligament (femoral attachment)
Also attached to the lateral meniscus
Posterior cruciate ligament (tibial attachment)
No SF, but lies close to the horn of the posterior meniscus, which acts as a PF; closely related to synovium
Posterior cruciate ligament (femoral attachment)
Also attached to the lateral meniscus
Lateral head of gastrocnemius
Tendon also arises from the knee joint capsule
Some fibers extend beyond the lesser trochanter to the adjacent part of the femur
Pes anserinus insertion
Subtendinous bursa present; no SF or PF, but thick periosteum
Adductor longus origin
Fuses with tendons of rectus abdominis and gracilis
Extensor hallucis longus insertion
Prominent SF in the deep surface of the tendon; articular cartilage acts as a PF; closely related to synovium
Flexor hallucis longus insertion
Fuses with fibrocartilaginous volar plate and articular cartilage acts as a PF for this; closely related to synovium
Extensor digitorum longus
SF in the deep surface of the tendon; articular cartilage acts as a PF; closely related to synovium
In sampling the entheses, 2 fine saw cuts were made into the bone, parallel to the long axis of the tendon, and 2 further cuts were made at right angles to the long axis, proximal and distal to the enthesis itself. Because of the size of the patellar tendon enthesis, only the central third of the attachment site was sampled. In accordance with our previously described protocol (12), all specimens were further fixed for at least 1 week in 10% neutral buffered formol saline before being decalcified in 5% nitric acid, dehydrated with graded alcohol, cleared with chloroform, and embedded in 58° C paraffin wax. Longitudinal sections of the enthesis and adjacent structures were cut at 8 μm, at 1-mm intervals throughout the block.
At each sample point, 16 sections were collected and mounted on 8 slides. Adjacent slides were stained with toluidine blue (to highlight the presence of fibrocartilage by its metachromasia) and Masson's trichrome (to illustrate the general architecture of the whole enthesis organ in the context of neighboring structures).
Enthesis organs can be broadly classified as joint related (hereinafter called “articular”) or extraarticular, according to whether the enthesis lies internal or external to the capsule of a synovial joint. We found that many entheses formed part of an enthesis organ—some simple, but others complex (see Table 1). In articular enthesis organs, the synovial membrane with which the enthesis is associated was a joint cavity. In extraarticular enthesis organs, it was that of a subtendinous bursa.
Articular enthesis organs.
The lateral collateral ligament and the popliteal tendon were shown to contribute to the formation of one of the most elaborate of articular enthesis organs (Figure 1). Their entheses were directly continuous with one another (Figure 1a), and the adjacent tendon pressed against the cartilage-lined, popliteal groove on the femur (Figure 1b). Occasionally, there was a hint of a sesamoid fibrocartilage on the deep aspect of the tendon within the popliteal groove (Figure 1c). There could also be a synovial, meniscoid fold in the interval between tendon and bone (Figure 1b). Such folds occasionally showed slight evidence of fibrocartilage differentiation (Figure 1d). Although part of the tendon was lined with synovium, this was absent where the tendon was in contact with the groove. However, detached fragments of synovium may be present in the joint cavity.
Another complex articular enthesis organ was that of the tibialis anterior (Figure 2). The tendon lay in a furrow on the medial side of the medial cuneiform, where it normally bifurcated into 2 slips—a deeper cuneiform slip and a more superficial, metatarsal slip (Figure 2a). At such attachments, the enthesis fibrocartilage of the cuneiform slip also served as a periosteal fibrocartilage for the metatarsal slip—this latter slip passed over the former. Indeed, adjacent to the cuneiform attachment site, the enthesis fibrocartilage was directly continuous with a periosteal cartilage/fibrocartilage covering a small bony elevation (Figure 2b). As a consequence of this complex arrangement, the deep aspect of the metatarsal slip showed some evidence of sesamoid fibrocartilage differentiation where it passed over the cuneiform enthesis (Figure 2a). Distal to that attachment site, the metatarsal slip replaced the joint capsule and thus contacted the cuneiform–metatarsal joint cavity directly. In this region, meniscoid synovial folds protruded into the joint space from the deep surface of the tendon (Figures 2b and c). Occasionally, the joint cavity extended between the 2 tendon slips as a bursal space (Figure 2a), and in some specimens, a bursa (not lined by synovium) extended into the narrow interval between the cuneiform slip and the bone; in others the region was filled with vascular, adipose tissue.
Where a tendon merged with a joint capsule, there was often a fairly simple articular enthesis organ. This consisted of the enthesis itself, a sesamoid fibrocartilage in the tendon adjacent to the attachment site, articular fibrocartilage covering a neighboring bone, and a joint cavity that allowed movement between sesamoid and articular fibrocartilages—the latter being functionally equivalent to periosteal fibrocartilage typical of that seen in the Achilles enthesis organ. Such a definition covers the enthesis organs of the digital extensor tendons (Figures 3a and b) and the collateral ligaments of the interphalangeal joints (Figures 3c and d). However, there may also be a meniscoid synovial fold extending into the joint cavity from the deep surface of the tendons, immediately distal to the sesamoid fibrocartilage (Figures 3a and b). In all such tendons, analogous to the retrocalcaneal bursa in the Achilles region, synovium was absent from the opposing surfaces of tendon and bone where these contact one another. A related type of enthesis organ is that where tendons reinforced, rather than replaced, joint capsules. This was exemplified by the insertion of abductor pollicis longus. Near this enthesis, a sesamoid fibrocartilage can be a prominent feature of the joint capsule. Stress can thus be dissipated from the tendinous to the capsular enthesis (and vice versa) by the continuity of the attachment sites. The relationship between enthesis and synovium is maintained because the latter lines the inside of the joint capsule.
The tibial attachment of the anterior cruciate ligament also formed part of a simple articular enthesis organ (Figure 4). It consisted of the enthesis itself, an articular cartilage/fibrocartilage that covered the lateral tubercle of the intercondylar eminence of the tibia (“tibial spine”), and the intervening cavity of the knee joint. There was no sesamoid fibrocartilage in the ligament where it passes over the tibial spine, but neither was there a synovial membrane covering the ligament in this region.
Extraarticular enthesis organs.
Extraarticular enthesis organs were exemplified by those associated with the biceps brachii and patellar insertional tendons (Figures 5a–c). A subtendinous bursa occupied the insertional angle between the tendon and the bone, and there was periosteal fibrocartilage of variable thickness near the attachment sites (Figures 6a and b). Although some fat was visible in association with both the biceps and the patellar tendon entheses (Figures 5a and c), much of Hoffa's fat-pad lay proximal to the level at which the specimens were removed from the cadavers for histologic processing. Despite the presence of a subtendinous bursa and a thick periosteum adjacent to the pes anserinus enthesis, no enthesis organ was present at this site (Figures 5d and 6c). There was no cartilage differentiation within the periosteum, and blood vessels were conspicuous (Figure 6c). Where both periosteal and sesamoid fibrocartilages were prominent at the insertion of the biceps brachii tendon, they largely replaced the synovial membrane of the intervening bursa in this region (Figure 6b). In the pes anserinus tendon, where neither fibrocartilage was present, the synovium was still visible (Figure 6c). At the insertion of biceps brachii, the fatty subsynovial tissue occasionally contained a small number of skeletal muscle fibers, together with associated “microtendons” (Figure 5b).
Sesamoid fibrocartilage was restricted to biceps brachii–and then only to specimens in which the periosteal fibrocartilage was also conspicuous (Figure 5a). Cadavers in which sesamoid and periosteal fibrocartilages were most prominent were those with a small area of tendon–bone attachment.
The Achilles insertion is a common site of disease in SpA and has rightly been described as the “première enthesis” (10). It forms part of a complex enthesis organ that comprises not only the insertion itself, but also adjacent tendon and bone fibrocartilage, together with a fat-pad, bursa, and synovium. The purpose of the present work was to investigate the extent to which other enthesis organs exist at diverse articular and extraarticular sites. We have shown that the concept of an “enthesis organ” can be applied to many (but not all) tendon and ligament attachments, and we thus argue that the concept is central to understanding of the spondylarthropathies. If stress is dissipated away from a bony insertion because of the existence of an enthesis organ, this can explain why pathologic changes are seen adjacent to entheses as well as at them, why subtendinous bursae are often affected in the disease (1, 2, 4, 13), and why bursitis can mimic enthesitis (14). It also illuminates the observation that periostitis is a common feature of SpA (15)—fibrocartilaginous periostea are a typical feature of many enthesis organs. Finally, the complexity of enthesis organs that are intimately associated with a synovial cavity may have implications regarding the mechanisms of synovitis in SpA.
We have described enthesis organs as being articular or extraarticular. All have in common the presence of sesamoid and/or periosteal cartilage or fibrocartilage juxtaposed to a synovial cavity and thus close to a synovial membrane. This either lines the joint cavity or forms part of a subtendinous bursa at the attachment site. Articular enthesis organs include those where the tendon/ligament fuses with a joint capsule (e.g., digital extensor tendons) or attaches inside a joint cavity (e.g., the tibial attachment of the anterior cruciate ligament and the insertion of popliteus). The presence of elaborate enthesis organs in direct association with synovial cavities, especially in joints such as the knee, enables better understanding of the anatomic basis of entheseal-related diseases, including SpA. We have shown, for example, that the femoral enthesis of the lateral collateral ligament merges imperceptibly with that of the popliteal tendon. This was also evident in the magnetic resonance imaging studies reported by Recondo et al (16). Consequently, the 2 structures, together with the associated synovium, form an enthesis organ as complex as that of the tibialis posterior (12). Evidently, stress could be dissipated between the ligament and the tendon enthesis, and thus what may seem to be a pathologic process restricted to an extrasynovial structure (the lateral collateral ligament enthesis) could affect the inside of the joint as well.
We have reported here that cartilage-covered, bony pulleys lie immediately adjacent to many entheses and often contribute to the formation of enthesis organs. Either the enthesis itself lies in a shallow depression below the level of the adjacent bone (i.e., so that the adjacent bone acts as a pulley) or there is a small bony protuberance next to the attachment site. The former is exemplified by the insertion of popliteus, and the latter by the tibial spine (intercondylar eminence) that contributes to the tibial enthesis organ of the anterior cruciate ligament, the radial tuberosity near the insertion of biceps brachii, and the unnamed tubercle near the attachment of the tibialis anterior. All such pulleys dissipate stress concentration so that the risk of wear and tear at entheses is reduced.
It has been proposed that the fundamental difference between rheumatoid arthritis and SpA is that synovitis in the former is primarily an immunologically mediated event, whereas in the latter it is secondary to liberation of proinflammatory mediators from sites of enthesitis. However, this hypothesis was proposed at a time when the enthesis organ concept had not yet been developed, and it was difficult to explain how focal insertional inflammation caused synovitis. Our results highlight the contribution of synovium to many enthesis organs, and we thus suggest that synovitis would be an anticipated consequence of enthesis organ inflammation. This applies to both articular and extraarticular enthesis organs. This is especially the case since the synovium, unlike the enthesis, contains macrophages. Like the Achilles enthesis organ, those described here in association with the insertions of the biceps brachii and patellar tendons lack a synovial lining in part of the bursa. This is not surprising since the tendon presses against the bone, and compression would occlude synovial vessels. It is exactly for this reason that synovium is absent over articular cartilage and at functional entheses (wrap-around regions of tendons ). Indeed, the local absence of synovium reinforces the similarities between many subtendinous bursae and typical synovial joints (9, 10). Consequently, deep infrapatellar bursitis and bicipital bursitis may involve fibrocartilage degeneration in the bursal walls, as well as synovitis.
In conclusion, this study shows that the concept of the enthesis organ is not unique to the Achilles insertion, but is more general: enthesis organs are present at many articular and extraarticular sites. The intimate relationship between enthesis organs and synovial cavities and the presence of enthesis organ components in joint capsules may have important implications for understanding the clinical pattern of SpA, including synovitis and extracapsular changes. It is important to acknowledge, however, that entheses do not always form parts of archetypal enthesis organs like that of the Achilles tendon, and this probably reflects local biomechanical factors that influence stress dissipation. Significantly, however, stress dissipation away from a single focused attachment site is virtually universal, because most tendons and ligaments fuse with adjacent structures or attach at more than one bony point.
We are grateful to E. Richter for technical assistance.