The
Journal of Pathology Voi. 127, No. 4 PATELLA DISPLACEMENT A N D OSTEOARTHROSIS O F THE K N E E J O I N T I N M I C E
MARKWALTON" Professorial Research Unit, Institute of Orthopaedics, Brockley Hill, Stanmore, Middlesex, and Department of Orthopaedic Surgery, University of Otago Medical School, Dunedin, New Zealand
PLATELXII THE knee joints of male mice of the inbred strain STR/ORT suffer from a very high incidence of osteoarthrosis (degenerative joint disease) (Walton, 1977a, b and c). A consistent characteristic of the disease is that degeneration of the articular surfaces appears only on the medial tibia1 and medial femoral condyles, almost invariably leaving the lateral condyles unaffected. In addition, both radiographically and histologically, there is a high statistical correlation between the incidence of spontaneous medial patella dislocation and osteoarthrosis (Walton, 1977a and b). However it was not clear in these previous studies as to which was the initial event, articular degeneration or patella displacement. Therefore an experimental approach was undertaken in order to clarify the situation. If the patellae of young male STR/ORT mice were surgically stabilised in their normal position, then the subsequent development or absence of osteoarthrosis in the femoro-tibia1 joint would help to define the role of patella displacement in the naturally-occurring disease. As a corollary, further evidence could be obtained by surgically produced and stabilised patella dislocation in mice of a strain of known low incidence of osteoarthrosis. MATERIALS AND METHODS 1. Patella stabilisation in male STRIORT mice Anaesthesia was induced with ether and maintained by NzO/halothane. The skin was opened over the anterior aspect of the left knee. Without opening the joint cavity, a triangular suture (5/0 silk) was threaded through the patella ligament immediately distal to the patella, passed along the medial border of the patella then through the quadriceps Received 30 June 1978; accepted 26 July 1978.
* Present address : Department of Orthopaedic Surgery, University of Otago Medical School,
P.O. Box 913, Dunedin, New Zealand. J. PATH.-VOL.
127 (1979)
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tendon and finally under the lateral collateral ligament (fig. la). In tying the suture, sufficient tension was applied to allow normal degrees of flexion and extension of the knee joint yet to hold the patella firmly in position during passive manipulation. The control right knee was treated in an identical manner but using a needle with no suture material. These operations were performed on 21 mice when they were 1 month old, i.e., at an age before naturally-occurring osteoarthrosis and patella dislocation had begun to develop (Walton, 1977a and b). Five months later the mice were killed with chloroform. Their knee joints were skinned then excised and subjected to radiological and histological investigations as described previously (Walton, 1977a and b).
FIG.1.-Diagrammatic representation of triangular sutures : (a) stabilising the patella of STR/ORT mice in its normal position and (b) maintainingmanually produced patella dislocationin CBAf
ORT mice.
2. Patella dislocation in male CBAIORT mice CBA/ORT mice have a very low incidence of osteoarthrosis in their knee joints (Walton, 1977a and b). A triangular suture was threaded similar t o that in the STR/ORT mice except that it supported the patella along its lateral border, attaching the bone to the medial collateral ligament (fig. lb). Before tying the suture the knee joint was fully extended and the patella manually dislocated medially. As with the STR/ORT mice the right knee served as a control. The operations were performed on 20 1-mth-old male CBA/ORT mice which were killed 5 mth later and their knee joints examined as previously described (Walton, 1977a and 6).
RESULTS 1. Patella stabilisation in STRIORT mice Throughout the post-operative period all of the 21 experimental male STRjORT mice showed normal locomotory behaviour with no reluctance to use either leg. After histological examination of the operated knees, nine were found to have patellae that had been successfully kept in place by the suture. Observations from the other 12 mice were discarded mostly because of either failure of the suture to prevent subluxation of the patella or because excessive tautness of the suture had produced a marked lateral subluxation of the patella.
Radiology Radiographs of the control right knees revealed a variety of degrees of patella dislocation. The presence of osteoarthrosis in many of these joints was
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indicated by abnormally thickened subchondral bone in the medial condyles. The radiographs of the experimental left knees invariably revealed large masses of ossified material around and above the patella (fig. 2). This new bone was markedly different in its form to the heterotopic bone found in naturallyoccurring osteoarthrotic joints in that it was much larger and was present on the outer surface of the patella. The form of the original patella was sometimes lost because of this new bone growth, but when it was discernible it appeared to be in its normal position relative to the femur. Two of the medial collateral ligaments of the control knees contained calcified material whereas in the experimental knees none mineralised: in contrast none of the control lateral collateral ligaments calcified whereas seven of the nine experimental knees had extensive calcification along much of the length of this ligament. Histology Serial sections of each knee were examined. The severity of osteoarthrosis in each joint was graded in accordance with a previously described schedule (Walton, 1977b). The results are presented in Table I. TABLEI Histological grading of osteoarthrosis in male STRIORT mouse knee joints with (experimental) or without (control)patella stabilisation No. of control knees
No. of experimental knees
n
3
1 2 3 4
2 3 1 0
9 0 0
Grade of severity of osteoarthrosis
0 0
Three of the control knees had no osteoarthrotic lesions (grade 0). Two further joints had early fibrillation but no loss of cartilage (grade 1). Three other control joints had lost significant amounts of uncalcified cartilage (grade 2) and in one joint the articular surface was at the level of the tidemark (grade 3). None of the nine experimental knee joints exhibited any histological signs of degenerative joint disease. In the right control joints the pathological changes were identical to those described previously (Walton, 1977b). The degree of patella displacement broadly reflected both the severity of articular degeneration and the extent of synovial metaplasia (i.e., heterotopic fibrosis, chondrification followed by calcification and ossification). In the left experimental joints the patella in its normal form was rarely seen (fig. 3). Often a short, thick bony spur had grown out laterally thus broadening the patella. Invariably there was thick inflammatory tissue around the suture thread on the medial side of the patella and on the lateral side of the joint. The thread was sometimes partially or totally enclosed in osseous tissue. Some isolated areas of calcification were present in synovial tissue, but the site, form and general appearance
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of these mineralised areas was not comparable to the heterotopic bony growths around the control joints. Due to the presence of the suture thread much of the lateral collateral ligament was engulfed in inflammatory tissue. However, this ligament was still discernible and usually contained a mass of thick calcified tissue in which there were small marrow spaces. In none of the joints was there inflammatory tissue over the femoro-tibia1or patello-femoral articulating surfaces. 2. Patella dislocation in CBAIORT mice One animal died during the post-operative period. Of the remaining mice all but five had an abnormal gait during which the operated knee had very limited flexion and extension during normal walking and when the animal was on its hind legs in the inquisitive or feeding posture. On post-mortem examination the mice with a normal gait were found to have normally positioned patellae, usually because the suture had slipped over the outer surface of the bone. Results from these individuals were eliminated from the study, observations from the remaining 14 mice are presented below. TABLEI1 Histological grading of osteoarthrosis in male CBAj 0 R T mouse knee joints with (experimental) or without (control)patella dislocation Grade of severity of osteoarthrosis 0 1
2 3 4
No. of control knees 14 0
0 0 0
No. of experimental knees 5 4 4 1 0
Radiology All the control joints appeared normal radiographically. The lateral view of the operated knees showed the distal end of the femur positioned well posteriorly on the tibia due to the high degree of flexion of the joint. A satisfactory anterior-posterior view was not obtained because this flexion deformity caused the shaft of the femur to be superimposed on the joint. Therefore no radiographic evidence was obtained on the occurrence of osteoarthrosis in the experiment joints. Histology Each knee joint was graded according to the severity of the histological signs of osteoarthrosis in the femoro-tibia1 articulation (Walton, 1977b). The resuIts are presented in Table 11. Osteoarthrosis was absent in all the control joints. Five of the operated knees had normal articular cartilage (grade 0), four had fibrillated surfaces (grade l), a further four had some loss of cartilage (grade 2, fig. 4), and one had almost total loss of uncalcified cartilage (grade 3). All the arthrotic joints
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PATELLA DISPLACEMENT
FIG. 2.-Lateral radiographic views of male STRjORT mouse knee joints: (a) after 5 mth with a surgically stabilised patella and (b) a non-operated joint with naturallyoccurring patella dislocation. x 12.
FIG.3.-Coronal
section through the knee joint of a STRjORT mouse after patella stabilisation for 5 mth. Osteoarthrosis is absent. (S = suture thread.) Haematoxylin and eosin. x 20.
FIG.4.-Coronal section through the medial condyles (tibia lower) of a CBA/ORT mouse after 5 mth of medial patella dislocation. Osteoarthrosis is present in the form of loss of cartilage and subchondral bone sclerosis. HE. Y 100. [facing page 168.
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had a lesion on their medial tibial condyle, however, one specimen also had a lesion on the lateral tibial condyle. In three joints the lesion was located adjacent to the cruciate ligaments (fig. 4), but in the other joints it was present either centrally on the condyle or on the outer edge. In eight joints the patella was positioned medial to the femur. Of these eight, four were associated with the most severe femoro-tibia1lesions whereas the other four had no cartilage degeneration. A further four patellae were only partially dislocated and they all had only the earliest stages of osteoarthrosis in their knee joints. The remaining patella, by the appearance of its eburnated articular surface, had been undergoing recurrent dislocation and the accompanying lesion on the medial tibial condyle showed loss of much of the uncalcified cartilage. Thus the degree of patella dislocation did not necessarily reflect the severity of the osteoarthrosis on the femoro-tibia1surface. The synovial tissue reaction varied considerably from those joints in which there was little change besides minor inflammation around the sutures, to those with thin heterotopic plaques of tissue containing mature bone which replaced much of the original synovial tissue. The patella was invariably deformed by the suture and the femoral groove became compressed laterally. DISCUSSION The results from this present study indicate that osteoarthrosis in the femorotibial joint of male STR/ORT mice is due to the usual tendency for the patella to dislocate medially. This was demonstrated by surgical prevention of medial displacement of the patella which resulted in the absence of the naturallyoccurring disease on the medial condyles. In addition, surgical production of medial patella dislocation in a non-arthrosis-prone mouse strain demonstrated that such a deformity can give rise to osteoarthrosis on the medial condyles of the knee joint over a similar time scale as the naturally-occurring disease in STR/OTR mice. Previous studies provide further evidence for the definite role of patella displacement in the development of osteoarthrosis in STRjORT mice (Walton, 1977a, b and c). Firstly the disease only arises on the medial condyles, i.e., on the side that is preferentially loaded due to patella displacement. Secondly, the incidence of patella subluxation and the incidence of osteoarthrosis of the medial tibial condyle showed a high statistical correlation in both radiological and histological studies. Considerable mechanical forces are applied through the human patella, especially when the knee joint is flexed under load (Paul, 1967; Maquet, 1970; Reilly and Martens, 1972). A similar situation must also apply to the mouse knee joint which is permanently carrying loads in the flexed position. Therefore if there is an alteration in the direction in which these forces are applied, then there will be significant consequences to the integrity of all of the tissues of the joint. With the patella subluxed or completely dislocated to the medial side, the forces generated by the quadriceps muscles will be preferentially applied to the medial condyles of the joint (Maquet; fig. 5). Ogata et al. (1977) applied a medial load of up to 1150 g across mobile rabbit knee joints by
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attaching a spring to the medial side. By 2 weeks the first signs of a degeneration of the cartilage appeared in the medial compartment of the joint. It would therefore appear possible that preferential loading of the medial side of the STR/ORT knee joints could lead to degeneration of the articular surfaces on that side.
FIG.5.-Diagrammatic
representation of the forces acting through the coronal plane of the mouse knee joint: (a) normally and (b) and (c) as the patella progressively dislocates.
In addition to an increased downward load on the medial condyles, the displaced patella of STR/ORT mice would apply a force to the side of the femur, thus constituting a lateral component to the resultant load (fig. 5b and c). Evidence that such a lateral force exists is seen histologically by (a) the growth of hyaline cartilage over the epicondyle of the femur in apposition to the displaced patella, showing that there must be articulation and load-bearing between the two bones; (b) a slight lateral subluxation of the femur relative to the tibia in severely arthrotic mice; (c) the lesion always appearing first on the medial tibia1 condyle adjacent to the cruciate ligaments (Walton, 1977b). The STR/ORT mouse strain originated from the STR/lN strain which has been extensively studied due to its high incidence of osteoarthrosis, especially
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in the male knee joints (reviewed by Walton, 1977~). However, in the original description of the disease in STR/lN mice, patella dislocation was only occasionally observed, though perhaps no specific study was made of this feature (Sokoloff, 1956). Only Wigley et ul. (1977) have specifically noted the position of the patella in murine osteoarthrosis and they found radiologically that displacement did not occur in NZY/B1 and PN mice which suffer from a high incidence of degenerative joint disease in the knee joint. The much higher incidence of the disease in STR/lN and STRjORT mice over all other strains (Sokoloff and Jay, 1956; Walton, 19773) is probably due to their predisposition for patella dislocation. Certainly in STRjORT mice the present study has shown that the osteoarthrosis is secondary to patella displacement rather than a primary disease (i.e., a disease of no known aetiology). Initiation of osteoarthrosis in CBA/ORT mice whose patellae had been surgically dislocated, demonstrated that alteration in the weight-bearing through the knee joint can give rise to articular degeneration of the medial tibia1 condyles over a similar time scale as in the naturally-occurring lesion in STR/ORT mice. The lesions in CBA/ORT joints were not all identical to those in the STR/ORT mice, but this was to be expected because dislocation of the patella was a sudden rather than slowly progressive event. Naturally-occurring patella dislocation in dogs can result in osteoarthrosis of the femoro-tibia1 joint (Kodituwakku, 1960). Bennet and Bauer (1937) produced patella dislocation in dogs but they did not record any observations on the femoro-tibia1joint. No explanation is offered as to the cause of patella dislocation in STR/ORT mice. The anatomy of the bones and quadriceps mechanisms were identical in both STR/ORT and CBA/ORT strains, as far as could be ascertained visually. SUMMARY
Surgical stabilisation of the normally medially-subluxing patella of STR/ ORT male mice, prevented the normal development of osteoarthrosis in the medial compartment of the femoro-tibia1 joint. Surgically produced medial dislocation of the patella in non-arthrosis-prone male CBA/ORT mice often gave rise to osteoarthrosis of the medial condyles. This, with further evidence from previous studies, strongly indicates that the high incidence of degenerative joint disease in male STR/ORT mice occurs because of a tendency of the patella to dislocate medially due to some unknown cause. The author is indebted to Mrs L. North and Mr D. Sayers for their technical assistance and to Dr Michael W. Elves for his advice and encouragement. This study was financed by the generosity of the Wellcome Trust through Dr Audrey U. Smith. REFERENCES BENNETT, G. A., AND BAUER,W. 1937. Joint changes resulting from patellar displacement and their relation to degenerative joint disease. J. Bone Jt. Surg., 19, 667. KODITCJWAKKU, G. E. 1960. Observations on some abnormalities of the stiflejoint in the dog: and an analysis of a series of fracture repairs in dogs including a bacteriological study of the peripheral blood of some of the fracture cases. Ph.D. Thesis, University of London.
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MAQUET,~. 1970. Biomechanicsand osteoarthritis of the knee. In 1lth Congrks International de Chirurgie Orthopedique et de Traumatologie. L. A., LESKER, P. A., AND SIMMONS, D. J. 1977. The effect of varus OGATA,K., WHITESIDE, stress on the moving rabbit knee. Clin. Orthop., 129, 313. PAUL,J. P. 1967. Forces transmitted by joints in the human body. Proc. Instn. Mech. Eng., 181, 35, 8. REILLY,D. T., AND MARTENS, M. 1972. Experimental analysis of the quadriceps muscle force and patello-femoral joint reaction force for various activities. Acta. Orthop. Scand., 43, 126. SOKOLOFF, L. 1956. Natural history of degenerativejoint disease in small laboratory animals. Pt. I. Pathologic anatomy of degenerative joint disease in mice. Arch. Path., 62, 118. SOKOLOFF, L., AND JAY,G. E. 1956. Natural history of degenerative joint disease in small laboratory animals. Pt. II. Epiphyseal maturation and osteoarthritis of the knee of mice of inbred strains. Arch. Path., 62, 129. M. 1977a. Degenerative joint disease in the mouse knee; radiological and morphoWALTON, logical observations. J. Path., 123, 97. WALTON, M. 19776. Degenerative joint disease in the mouse knee; histological observations. J. Path., 123, 109. M. 1977c. Degenerative joint disease in the mouse knee joint; scanning electron WALTON, microscopy. J. Path., 123, 211. K. G., MAULE,R., AND REAY,B. R. 1977. Degenerative WIGLEY,R. D., COUCHMAN, arthritis in mice. Study of age and sex frequency in various strains with a genetic study of NZB/Bl, NZY/Bl, and hybrid mice. Ann. Rheum. Dis.,36, 249.
Journal of Pathology Voi. 127, No. 4 PATELLA DISPLACEMENT A N D OSTEOARTHROSIS O F THE K N E E J O I N T I N M I C E
MARKWALTON" Professorial Research Unit, Institute of Orthopaedics, Brockley Hill, Stanmore, Middlesex, and Department of Orthopaedic Surgery, University of Otago Medical School, Dunedin, New Zealand
PLATELXII THE knee joints of male mice of the inbred strain STR/ORT suffer from a very high incidence of osteoarthrosis (degenerative joint disease) (Walton, 1977a, b and c). A consistent characteristic of the disease is that degeneration of the articular surfaces appears only on the medial tibia1 and medial femoral condyles, almost invariably leaving the lateral condyles unaffected. In addition, both radiographically and histologically, there is a high statistical correlation between the incidence of spontaneous medial patella dislocation and osteoarthrosis (Walton, 1977a and b). However it was not clear in these previous studies as to which was the initial event, articular degeneration or patella displacement. Therefore an experimental approach was undertaken in order to clarify the situation. If the patellae of young male STR/ORT mice were surgically stabilised in their normal position, then the subsequent development or absence of osteoarthrosis in the femoro-tibia1 joint would help to define the role of patella displacement in the naturally-occurring disease. As a corollary, further evidence could be obtained by surgically produced and stabilised patella dislocation in mice of a strain of known low incidence of osteoarthrosis. MATERIALS AND METHODS 1. Patella stabilisation in male STRIORT mice Anaesthesia was induced with ether and maintained by NzO/halothane. The skin was opened over the anterior aspect of the left knee. Without opening the joint cavity, a triangular suture (5/0 silk) was threaded through the patella ligament immediately distal to the patella, passed along the medial border of the patella then through the quadriceps Received 30 June 1978; accepted 26 July 1978.
* Present address : Department of Orthopaedic Surgery, University of Otago Medical School,
P.O. Box 913, Dunedin, New Zealand. J. PATH.-VOL.
127 (1979)
165
N
MARK WALTON
166
tendon and finally under the lateral collateral ligament (fig. la). In tying the suture, sufficient tension was applied to allow normal degrees of flexion and extension of the knee joint yet to hold the patella firmly in position during passive manipulation. The control right knee was treated in an identical manner but using a needle with no suture material. These operations were performed on 21 mice when they were 1 month old, i.e., at an age before naturally-occurring osteoarthrosis and patella dislocation had begun to develop (Walton, 1977a and b). Five months later the mice were killed with chloroform. Their knee joints were skinned then excised and subjected to radiological and histological investigations as described previously (Walton, 1977a and b).
FIG.1.-Diagrammatic representation of triangular sutures : (a) stabilising the patella of STR/ORT mice in its normal position and (b) maintainingmanually produced patella dislocationin CBAf
ORT mice.
2. Patella dislocation in male CBAIORT mice CBA/ORT mice have a very low incidence of osteoarthrosis in their knee joints (Walton, 1977a and b). A triangular suture was threaded similar t o that in the STR/ORT mice except that it supported the patella along its lateral border, attaching the bone to the medial collateral ligament (fig. lb). Before tying the suture the knee joint was fully extended and the patella manually dislocated medially. As with the STR/ORT mice the right knee served as a control. The operations were performed on 20 1-mth-old male CBA/ORT mice which were killed 5 mth later and their knee joints examined as previously described (Walton, 1977a and 6).
RESULTS 1. Patella stabilisation in STRIORT mice Throughout the post-operative period all of the 21 experimental male STRjORT mice showed normal locomotory behaviour with no reluctance to use either leg. After histological examination of the operated knees, nine were found to have patellae that had been successfully kept in place by the suture. Observations from the other 12 mice were discarded mostly because of either failure of the suture to prevent subluxation of the patella or because excessive tautness of the suture had produced a marked lateral subluxation of the patella.
Radiology Radiographs of the control right knees revealed a variety of degrees of patella dislocation. The presence of osteoarthrosis in many of these joints was
167
PATELLA DISPLACEMENT
indicated by abnormally thickened subchondral bone in the medial condyles. The radiographs of the experimental left knees invariably revealed large masses of ossified material around and above the patella (fig. 2). This new bone was markedly different in its form to the heterotopic bone found in naturallyoccurring osteoarthrotic joints in that it was much larger and was present on the outer surface of the patella. The form of the original patella was sometimes lost because of this new bone growth, but when it was discernible it appeared to be in its normal position relative to the femur. Two of the medial collateral ligaments of the control knees contained calcified material whereas in the experimental knees none mineralised: in contrast none of the control lateral collateral ligaments calcified whereas seven of the nine experimental knees had extensive calcification along much of the length of this ligament. Histology Serial sections of each knee were examined. The severity of osteoarthrosis in each joint was graded in accordance with a previously described schedule (Walton, 1977b). The results are presented in Table I. TABLEI Histological grading of osteoarthrosis in male STRIORT mouse knee joints with (experimental) or without (control)patella stabilisation No. of control knees
No. of experimental knees
n
3
1 2 3 4
2 3 1 0
9 0 0
Grade of severity of osteoarthrosis
0 0
Three of the control knees had no osteoarthrotic lesions (grade 0). Two further joints had early fibrillation but no loss of cartilage (grade 1). Three other control joints had lost significant amounts of uncalcified cartilage (grade 2) and in one joint the articular surface was at the level of the tidemark (grade 3). None of the nine experimental knee joints exhibited any histological signs of degenerative joint disease. In the right control joints the pathological changes were identical to those described previously (Walton, 1977b). The degree of patella displacement broadly reflected both the severity of articular degeneration and the extent of synovial metaplasia (i.e., heterotopic fibrosis, chondrification followed by calcification and ossification). In the left experimental joints the patella in its normal form was rarely seen (fig. 3). Often a short, thick bony spur had grown out laterally thus broadening the patella. Invariably there was thick inflammatory tissue around the suture thread on the medial side of the patella and on the lateral side of the joint. The thread was sometimes partially or totally enclosed in osseous tissue. Some isolated areas of calcification were present in synovial tissue, but the site, form and general appearance
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of these mineralised areas was not comparable to the heterotopic bony growths around the control joints. Due to the presence of the suture thread much of the lateral collateral ligament was engulfed in inflammatory tissue. However, this ligament was still discernible and usually contained a mass of thick calcified tissue in which there were small marrow spaces. In none of the joints was there inflammatory tissue over the femoro-tibia1or patello-femoral articulating surfaces. 2. Patella dislocation in CBAIORT mice One animal died during the post-operative period. Of the remaining mice all but five had an abnormal gait during which the operated knee had very limited flexion and extension during normal walking and when the animal was on its hind legs in the inquisitive or feeding posture. On post-mortem examination the mice with a normal gait were found to have normally positioned patellae, usually because the suture had slipped over the outer surface of the bone. Results from these individuals were eliminated from the study, observations from the remaining 14 mice are presented below. TABLEI1 Histological grading of osteoarthrosis in male CBAj 0 R T mouse knee joints with (experimental) or without (control)patella dislocation Grade of severity of osteoarthrosis 0 1
2 3 4
No. of control knees 14 0
0 0 0
No. of experimental knees 5 4 4 1 0
Radiology All the control joints appeared normal radiographically. The lateral view of the operated knees showed the distal end of the femur positioned well posteriorly on the tibia due to the high degree of flexion of the joint. A satisfactory anterior-posterior view was not obtained because this flexion deformity caused the shaft of the femur to be superimposed on the joint. Therefore no radiographic evidence was obtained on the occurrence of osteoarthrosis in the experiment joints. Histology Each knee joint was graded according to the severity of the histological signs of osteoarthrosis in the femoro-tibia1 articulation (Walton, 1977b). The resuIts are presented in Table 11. Osteoarthrosis was absent in all the control joints. Five of the operated knees had normal articular cartilage (grade 0), four had fibrillated surfaces (grade l), a further four had some loss of cartilage (grade 2, fig. 4), and one had almost total loss of uncalcified cartilage (grade 3). All the arthrotic joints
PLATELXII
WALTON
PATELLA DISPLACEMENT
FIG. 2.-Lateral radiographic views of male STRjORT mouse knee joints: (a) after 5 mth with a surgically stabilised patella and (b) a non-operated joint with naturallyoccurring patella dislocation. x 12.
FIG.3.-Coronal
section through the knee joint of a STRjORT mouse after patella stabilisation for 5 mth. Osteoarthrosis is absent. (S = suture thread.) Haematoxylin and eosin. x 20.
FIG.4.-Coronal section through the medial condyles (tibia lower) of a CBA/ORT mouse after 5 mth of medial patella dislocation. Osteoarthrosis is present in the form of loss of cartilage and subchondral bone sclerosis. HE. Y 100. [facing page 168.
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had a lesion on their medial tibial condyle, however, one specimen also had a lesion on the lateral tibial condyle. In three joints the lesion was located adjacent to the cruciate ligaments (fig. 4), but in the other joints it was present either centrally on the condyle or on the outer edge. In eight joints the patella was positioned medial to the femur. Of these eight, four were associated with the most severe femoro-tibia1lesions whereas the other four had no cartilage degeneration. A further four patellae were only partially dislocated and they all had only the earliest stages of osteoarthrosis in their knee joints. The remaining patella, by the appearance of its eburnated articular surface, had been undergoing recurrent dislocation and the accompanying lesion on the medial tibial condyle showed loss of much of the uncalcified cartilage. Thus the degree of patella dislocation did not necessarily reflect the severity of the osteoarthrosis on the femoro-tibia1surface. The synovial tissue reaction varied considerably from those joints in which there was little change besides minor inflammation around the sutures, to those with thin heterotopic plaques of tissue containing mature bone which replaced much of the original synovial tissue. The patella was invariably deformed by the suture and the femoral groove became compressed laterally. DISCUSSION The results from this present study indicate that osteoarthrosis in the femorotibial joint of male STR/ORT mice is due to the usual tendency for the patella to dislocate medially. This was demonstrated by surgical prevention of medial displacement of the patella which resulted in the absence of the naturallyoccurring disease on the medial condyles. In addition, surgical production of medial patella dislocation in a non-arthrosis-prone mouse strain demonstrated that such a deformity can give rise to osteoarthrosis on the medial condyles of the knee joint over a similar time scale as the naturally-occurring disease in STR/OTR mice. Previous studies provide further evidence for the definite role of patella displacement in the development of osteoarthrosis in STRjORT mice (Walton, 1977a, b and c). Firstly the disease only arises on the medial condyles, i.e., on the side that is preferentially loaded due to patella displacement. Secondly, the incidence of patella subluxation and the incidence of osteoarthrosis of the medial tibial condyle showed a high statistical correlation in both radiological and histological studies. Considerable mechanical forces are applied through the human patella, especially when the knee joint is flexed under load (Paul, 1967; Maquet, 1970; Reilly and Martens, 1972). A similar situation must also apply to the mouse knee joint which is permanently carrying loads in the flexed position. Therefore if there is an alteration in the direction in which these forces are applied, then there will be significant consequences to the integrity of all of the tissues of the joint. With the patella subluxed or completely dislocated to the medial side, the forces generated by the quadriceps muscles will be preferentially applied to the medial condyles of the joint (Maquet; fig. 5). Ogata et al. (1977) applied a medial load of up to 1150 g across mobile rabbit knee joints by
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attaching a spring to the medial side. By 2 weeks the first signs of a degeneration of the cartilage appeared in the medial compartment of the joint. It would therefore appear possible that preferential loading of the medial side of the STR/ORT knee joints could lead to degeneration of the articular surfaces on that side.
FIG.5.-Diagrammatic
representation of the forces acting through the coronal plane of the mouse knee joint: (a) normally and (b) and (c) as the patella progressively dislocates.
In addition to an increased downward load on the medial condyles, the displaced patella of STR/ORT mice would apply a force to the side of the femur, thus constituting a lateral component to the resultant load (fig. 5b and c). Evidence that such a lateral force exists is seen histologically by (a) the growth of hyaline cartilage over the epicondyle of the femur in apposition to the displaced patella, showing that there must be articulation and load-bearing between the two bones; (b) a slight lateral subluxation of the femur relative to the tibia in severely arthrotic mice; (c) the lesion always appearing first on the medial tibia1 condyle adjacent to the cruciate ligaments (Walton, 1977b). The STR/ORT mouse strain originated from the STR/lN strain which has been extensively studied due to its high incidence of osteoarthrosis, especially
PATELLA DISPLACEMENT
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in the male knee joints (reviewed by Walton, 1977~). However, in the original description of the disease in STR/lN mice, patella dislocation was only occasionally observed, though perhaps no specific study was made of this feature (Sokoloff, 1956). Only Wigley et ul. (1977) have specifically noted the position of the patella in murine osteoarthrosis and they found radiologically that displacement did not occur in NZY/B1 and PN mice which suffer from a high incidence of degenerative joint disease in the knee joint. The much higher incidence of the disease in STR/lN and STRjORT mice over all other strains (Sokoloff and Jay, 1956; Walton, 19773) is probably due to their predisposition for patella dislocation. Certainly in STRjORT mice the present study has shown that the osteoarthrosis is secondary to patella displacement rather than a primary disease (i.e., a disease of no known aetiology). Initiation of osteoarthrosis in CBA/ORT mice whose patellae had been surgically dislocated, demonstrated that alteration in the weight-bearing through the knee joint can give rise to articular degeneration of the medial tibia1 condyles over a similar time scale as in the naturally-occurring lesion in STR/ORT mice. The lesions in CBA/ORT joints were not all identical to those in the STR/ORT mice, but this was to be expected because dislocation of the patella was a sudden rather than slowly progressive event. Naturally-occurring patella dislocation in dogs can result in osteoarthrosis of the femoro-tibia1 joint (Kodituwakku, 1960). Bennet and Bauer (1937) produced patella dislocation in dogs but they did not record any observations on the femoro-tibia1joint. No explanation is offered as to the cause of patella dislocation in STR/ORT mice. The anatomy of the bones and quadriceps mechanisms were identical in both STR/ORT and CBA/ORT strains, as far as could be ascertained visually. SUMMARY
Surgical stabilisation of the normally medially-subluxing patella of STR/ ORT male mice, prevented the normal development of osteoarthrosis in the medial compartment of the femoro-tibia1 joint. Surgically produced medial dislocation of the patella in non-arthrosis-prone male CBA/ORT mice often gave rise to osteoarthrosis of the medial condyles. This, with further evidence from previous studies, strongly indicates that the high incidence of degenerative joint disease in male STR/ORT mice occurs because of a tendency of the patella to dislocate medially due to some unknown cause. The author is indebted to Mrs L. North and Mr D. Sayers for their technical assistance and to Dr Michael W. Elves for his advice and encouragement. This study was financed by the generosity of the Wellcome Trust through Dr Audrey U. Smith. REFERENCES BENNETT, G. A., AND BAUER,W. 1937. Joint changes resulting from patellar displacement and their relation to degenerative joint disease. J. Bone Jt. Surg., 19, 667. KODITCJWAKKU, G. E. 1960. Observations on some abnormalities of the stiflejoint in the dog: and an analysis of a series of fracture repairs in dogs including a bacteriological study of the peripheral blood of some of the fracture cases. Ph.D. Thesis, University of London.
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MAQUET,~. 1970. Biomechanicsand osteoarthritis of the knee. In 1lth Congrks International de Chirurgie Orthopedique et de Traumatologie. L. A., LESKER, P. A., AND SIMMONS, D. J. 1977. The effect of varus OGATA,K., WHITESIDE, stress on the moving rabbit knee. Clin. Orthop., 129, 313. PAUL,J. P. 1967. Forces transmitted by joints in the human body. Proc. Instn. Mech. Eng., 181, 35, 8. REILLY,D. T., AND MARTENS, M. 1972. Experimental analysis of the quadriceps muscle force and patello-femoral joint reaction force for various activities. Acta. Orthop. Scand., 43, 126. SOKOLOFF, L. 1956. Natural history of degenerativejoint disease in small laboratory animals. Pt. I. Pathologic anatomy of degenerative joint disease in mice. Arch. Path., 62, 118. SOKOLOFF, L., AND JAY,G. E. 1956. Natural history of degenerative joint disease in small laboratory animals. Pt. II. Epiphyseal maturation and osteoarthritis of the knee of mice of inbred strains. Arch. Path., 62, 129. M. 1977a. Degenerative joint disease in the mouse knee; radiological and morphoWALTON, logical observations. J. Path., 123, 97. WALTON, M. 19776. Degenerative joint disease in the mouse knee; histological observations. J. Path., 123, 109. M. 1977c. Degenerative joint disease in the mouse knee joint; scanning electron WALTON, microscopy. J. Path., 123, 211. K. G., MAULE,R., AND REAY,B. R. 1977. Degenerative WIGLEY,R. D., COUCHMAN, arthritis in mice. Study of age and sex frequency in various strains with a genetic study of NZB/Bl, NZY/Bl, and hybrid mice. Ann. Rheum. Dis.,36, 249.
