Subchondral Bone Changes in Patients with Early Degenerative Joint Disease

Transcription

1 Subchondral Bone Changes in Patients with Early Degenerative Joint Disease Eric L. Radin, lgor L. Paul and Marc J. Tolkoff The relationship between early degeneration of articular cartilage and the energyabsorbing abilities of its subchondral bony bed was studied in specimens obtained at autopsy from the knees of 43 male patients. Subchondral bone plugs from patients whose cartilage had only mild mucopolysaccharide loss absorbed relatively less energy on impact than the normals. There was no apparent difference in energy absorption among the bone plugs of the normal, the moderate, and the markedly altered cartilage groups. These changes were not age related. The etiology of degenerative joint disease has eluded investigators for centuries. Contrary to classical teachings, our work on the ability of whole joints to attenuate the peak force occurring during rapidly applied loading has suggested that bone and soft tissues play a larger part than synovial fluid and cartilage in attenuating such forces (1). On the basis of these results, it is attractive to hypothesize, that if degener- itive joint disease is related to the joint s inability to handle large loads, alterations in bone could significantly affect the pressures exerted on articular cartilage. The primary change in degenerative joint disease could be, therefore, in the bone. To test this hypothesis, the mechanical properties of cancellous bone from a small group of patients with varying degrees of degenerative joint disease were studied. From the Orthopedic Research Laboratories, Harvard Medical School, Massachusetts General Hospital, Boston, Mass. ERIC L. RADIN, MD: Instructor in Orthopedic Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Mass 02114; Special Post- Doctoral Fellow of the National Institute of Arthritis and Metabolic Diseases; Lecturer, Department of Mechanical Engineering, Massachusetts Institute of Technology. ICOR L. PAUL, DSc: Associate Professor of Mechanical Engineering, Massachusetts Institute MATERIALS AND METHODS Subchondral bone plugs, /4 inch in diameter, were obtained at autopsy from identical spots on the weight-bearing portion of the medial femoral condyle of the right knee of 43 male patients. These patients had no history of joint disease, were from 28 to 92 years old and weighed from 108 to 184 lb. Adjacent plugs were taken for histologic examination. They were immediately fixed in a$tated Bouin s solution for 12 hr at 4 O C, then of Technology, Cambridge, Mass. MARC J. TOLKOFF, decalcified in the cold in neutral buffered EDTA Senior Student, Department of Applied Physics, Harvard College, Cambridge, Mass. and stained with safranin red-0, a stain specific for Reprint requests should be addressed to Dr. mucopolysaccharides (2). The slides were coun- Radin. terstained with methyl green. Submitted for publication Dec 15, 1969; accepted The plugs for mechanical testing were immedi- March 3, ately frozen (unfixed), stored and thawed just 400 Arthritis and Rheumatism, Vol. 13, No. 4 (July-August 1970)

2 SUBCHONDRAL BONE CHANGES before testing. At that time, the articular cartilage of the plugs was removed in a lathe. The plugs were then reversed in the collet, and subchondral bone from the apposite (nonarticular) end was machined off until the plug was inches thick. Slow machining speeds were used to prevent heating the specimens. All plugs were flat on both ends and uniform in size. They were then subjected to impact loading by reproducibly dropping weight on them. The resulting deflection and transmitted force were recorded. This technic has been described previously (1,3). The impact data were recorded by tracing transmitted force and deflection with time. To ubtain an initial relative measure of energy stored and dissipated by the specimen during dynamic loading, the force curves were approximated as straight lines to their initial peak; the deflection curves were approximated similarly to the point in time when force curve peak occurred. A triangle was then constructed, using the height of deflection as its base, and the maximum force as its height. Half the product of these values is equal to the area of this triangle. This value is an approximation of the energy dissipated by the specimens, since energy equals the integral of force times deformation. The technic used for this calculation is sketched in Fig 1 and 2. An absolute measure of energy absorbed or dissipated by the specimen would involve integrating under the whole force curve for multiple, small intervals of deformation. The relative relationships between the values appear to be unaffected by the simple approximation. The patients were divided into 4 groups by the microscapic appearance of their articular cartilages: (1) normal; (2) slight mucopolysaccharide CMPS) loss from surface areas with safranin staining; (3) moderate MPS loss with occasional chondrocyte cloning; and (4) marked MPS loss associated with cartilage thinning, fibrillation and frequent chondrocyte cloning (Fig 3-6). All histologic material was handled identically, and objective evaluation was encouraged by using code numbers to identify the slides. RESULTS By histologic examination, there were 15 patients with normal joints (Group 0), 6 patients with slight MPS loss (Group I), 15 patients with moderate MPS loss (Group 11) and 7 patients with marked MPS loss and obvious fibrillation of cartilage (Group 111). There was no correlation between either age or weight and degree of cartilage degeneration. Approximations of impact energies at '/4 and v8 inch droppings of the weight are presented in Table 1 and 2. The difference in mean energy approximations has been subjected to Student's t tests, and its significance reported in these tables as well. It can be seen that any pairing involving Group I shows a significant difference (p <.Ol), and that with one exception there Fig 1. The use of actual force and deflection traces to approximate the relative energy absorption of the bone plugs at the time peak dynamic force is attained. Line a represents peak dynamic force: part b of that line represents deflection at that time. An approximation of both upward slopes of force and deflection traces by straight lines (for force is line c) is implied with this technic. OEFL ECT/ON TRACE TIME Arthritis and Rheumatism, Vol. 13, No. 4 (July-August 1970) 401

3 RADIN AL w 0 U B Y a w a DEFLECTION AT TIME OF PEAK DYNAMIC FORCE Fig 2. The approximation of energy absorbed by the specimens is the area of a triangle formed by using lines a and b from Fig 1. are no significant differences (p <.lo) between other pairs. The energy losses during the impact of specimens could be due in prt to nonelastic deformation of surface irregularities, as the plunger comes in contact with the specimen surfaces, and to the sliding and friction forces of realignment of the bone plug, plug holder and weight during impact. Consistency, or the elimination of factors other than those due to the energy dissipated within the specimens themselves, was established by the complete reproducibility 01 force and deflection traces after repeated impacts of the same specimen and the removal and replacement of specimens. Therefore, the results presented here do represent valid comparisons of relative energies associated with the specimens themselves. DISCUSSION Any attempt to correlate the mechanical properties of a biologic tissue with its physical appearance is always difficult. The mechanical behavior of these substances is complex, and the anatomic classification is, at best, very subjective. We were interested in changes in mechanical properties that might take place very early in the come of degenerative joint disease. The loss of MPS from the surlace of the cartilage (just below the Fig 3-6. Safranin red-0 and methyl green stained articular cartilage. x 40 Fig 3. Normal (Group 0). Fig 4. Slight mucopolysaccharide (MPS) loss from the surface areas (Group I). Fig 5. Moderate MPS loss with occasional chondrocyte cloning (Group 11). Fig 6. Marked MPS loss associated with cartilage thinning, fibrillation and frequent chondrocyte cloning (Group 111). 402 Arthritis and Rheumatism, Vol. 13, No. 4 (July-August 1970)

4 ~~~ ~ SUBCHONDRAL BONE CHANGES Table 1. Approximate Impact Energies of Subchondral Bone Plugs Subjected to Weight Dropped W Inch No. speci- SD Group mens Range Mean (N-1) SE I I Ill Total 43 II &I Groups Diff. in compared means t N-1 p O&I <.oi 0 &I NS 0 & Ill NS I &II <.oi I & Ill c & NS 0 & II + Ill NS I & I1 Ill <.a1 Table 2. Approximate Impact Energies of Subchondral Bone Plugs Subjected to Weight Dropped Inch No. speci- SD Group mens Range Mean (N-1) SE ~ 0 15 I 6 II 15 Ill 7 Total 43 II & Ill 22 Groups compared 0841 O&II 0 &Ill I &II I & Ill II &Ill 0 & II + Ill I & I t + Ill Diff. in means t N P <.01 NS <.05 <.01 <.01 NS ~- NS 8 <.01 lamina splenrlens) is the best presently available measure of early degenerative joint disease (4,5). The safranin-0 red staining technic, as all quantitative histologic methods, is subject to multiple technical errors; still however, it appears to be the best presently available way to measure geographic MPS loss. Rosenberg (2) has lound this technic to be quantitative enough to be substituted for MPS chemical determinations. In order to minimize error, the histologic preparation of the specimens was done by one technician in a uniform fashion, and all slides were coded and read by one of us without knowledge of the mechanical behavior results. The well-known effects of acid decalcifying agents on mucopolysaccliarides (6) were averted by using neutral buffered EDTA. One measure of tissue response to suddenly applied forces is its ability to absorb energy. If the bone plug is considered to be compliant (3), the force transducer located below the plug actually measures the instantaneous force transmitted through the plug (assuming neglibile acceleration of the specimen). A linear-variable differential transducer gives extremely accurate measurements of deformation in the vertical plane. The plugs were all machined to equivalent size, and as closely as possible, obtained from the same spot in all of the knees. Although the deformation of the bone plugs, which obviously takes place in the horizontal plane, is not measured in this test system, it is felt that the data reported, although relative, is more than adequate for relating the test specimens to each other. Assuming the physiologic load on cartilage is approximately 500 lb per square inch (7, 8), the impact forces applied in this experiment are well within this range. (They averaged 30 Ib on the high (g inch) drops; Arthritis and Rheumatism, Vol. 13, No. 4 (July-August 1970) 403

5 the plugs had a radius of '/s inch and an area of square inches.) Extreme forces were not applied in these tests to prevent crushing the bone plugs. The lack of correlation between age and degree of degenerative joint disease is not surprising if one remembers that only patients without joint signs or symptoms were included in this study; thus, our sample was very biased. For the same reason, no conclusions can be drawn from the lack of correlation between weight and joint degenera tion. The striking finding in this study was the significant drop in energy absorption which occurred only in the Group I patients, those with the earliest degenerative changes. Except in the '/4 inch impact tests, where a lower but significant difference was found between normal and obviously arthritic patients (Group 111), the energy-absorbing abilities of subchondral bone returned to near normal values after the earliest stages of degeneration passed and moderate alterations occurred. Attempts have been made to relate the decreased energy-absorbing abilities of subchondral bone in early degenerative joint disease to the relative amount and density of such bone in uniform-sized undecalcified sections. No significant differences in these parameters could be demonstrated among the bone specimens of the various groups of patients. Further attempts to characterize the trabecular bone are underway. Since the number of patients in each group was so small, it is possible that we have encountered a statistical accident. Wide variations in the compressive strength of cancellous bone from normal individuals have been reported (9). But, assuming that the data presented here do represent the true state of the subchondral bone in early degenerative joint disease, the dimin- ished energy absorption ability of subchondral bone means that more energy must be absorbed by the remaining parts of the skeletal system. Thus, more stress is placed on the cartilage, cortical bone and soft tissues. It has previously been shown that cartilage attenuates very little of the impact load applied to whole joints and, that as a tissue, its relative thinness prevents it from being a major energy absorber (1). Cartilage would, therefore, be very suscep tible to an increase in stress, which it would be unable to handle. Although the exact temporal sequence is unclear, the diminution in the energy-absorbing abilities of subchondral bone seems to be associated only with early cartilage degeneration. Perhaps, the bone changes come first. ACKNOWLEDGMENTS We thank Professor Robert M. Rose for aid ing us in the interpretation of our data. REFERENCES 1. Radin EL, Paul IL: Does cartilage compliance reduce skeletal impact loads? The relative force attenuating,properties of articular cartilage, synovial fluid, periarticular soft tissues, and bone. Arthritis Rheum 13: , Rosenberg LC: Chemical basis for histological use of Safranin-0 in the study of articular cartilage (in preparation). Presented to the Orthopedic Research Society, January 1970, Chicago, I11 3. Radin EL, Paul IL, Lowy M: A comparison of the force transmitting properties of subchondral bone and articular cartilage. J Bone Joint Surg 52A: , Barland P, Janis R, Sandson J: Immunofluorescent studies of human articular cartilage. Ann Rheum Dis 25: , Bollet AJ: Connective tissue polysaccharide metabolism and the pathogenesis of osteo- 404 Arthritis and Rheumatism, Vol. 13, No. 4 (July-August 1970)

6 SUBCHONDRAL BONE CHANGES arthritis. Advances Intern Rled 13:53-60, Schajowicz F, Cabrini RL: The efiects of acids (decalcifying solutions) and enzymes on the histo-chemical behaviour of bone and cartilage. J Histochem Cytochem 3: , Paul, JP: Forces transmitted by joints in the human body. Symposium on Lubrication and Wear in Living and Artificial Joints. Inst Medi Eng, London, 1967, p Maroudas A, Bullough P, Swanson SAV, et al: The permeability of articular car-,tilage. J Bone Joint Surg 50B:16&177, Weaver JK, Chalmers J: Cancellous bone: its strength and changes with aging and an evaluation of some methods of measuring its mineral content. J Bone Joint Surg 48A: , 1966 Mhritis and Rheumatism, Vol. 13, No. 4 (July-August 1970) 405