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ROLE OF MECHANICAL FACTORS IN PATHOGENESIS OF PRIMARY OSTEOARTHRITIS
519
of
Hypothesis ROLE OF MECHANICAL FACTORS IN PATHOGENESIS OF PRIMARY OSTEOARTHRITIS IGOR L. PAUL ERIC L. RADIN ROBERT M. ROSE Research Laboratories, Harvard Medical School, Orthopedic Children’s Hospital Medical Center, Boston, Massachusetts 02115, and Department of Mechanical Engineering and Department of Metallurgy and Materials Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
Studies of the relation between joint function and mechanical stress have led to a revival of the old concept that primary osteoarthritis is actually a wearing out of joints. Recent experimental evidence suggests that joints can wear out by repetitive impulsive loading, rather than by rubbing. This new mechanistic approach is compatible with the pathology of, and clinical experience with, the disease.
Sum ary
THE concept that osteoarthritis is simply a wearing of joints, a natural ageing and attrition of Nature’s bearings subjected to years of long and hard use, has almost completely fallen from favour over the past two decades. Articular cartilage has been shown in the adult to be an active and viable tissue quite capable of producing excessive amounts of mucoout
1
polysaccharide and collagen in response to injury. Adult articular cartilage in and of itself does not mechanically change with age.2 The attrition of articular cartilage in areas systematically deprived of load-bearing has been shown to be unrelated to the development of joint degeneration,3,4 and it has been found that joints move even under high loads with amazingly low coefficients of friction, rendering almost completely untenable the possibility that joints wear
5 away from back-and-forth motion.5
Observa-
limited to clinical experience, demonstrates time and again individuals who have done hard work all their lives without manifestations of joint degeneration. The disease has a predilection for womenwho in general seem to subject their joints to much less stress. Furthermore, the pattern
tion, certainly
1. 2. 3.
4. 5. 6. 7. 8. 9. 10. 11.
not
Bourne, J. G., Collier, H. O. J., Somers, C. F. Lancet, 1952, i, 1225. Roth, F., Wüthrick, H. Br. J. Anœsth. 1969, 41, 311. Mathias, J. A., Evans Prosser, C. D. G. Prog. Anœsth. 1970, p. 1153. Kelman, G. R., Kennedy, R. R. Br. J. Anœsth. 1971, 43, 335. Strunin, L., Strunin, J. M., Layton, J., Sim, A. W., Simpson, B. R. Unpublished. Bolger, L., Brittain, R. T., Jack, D., Jackson, M. R., Martin, L. E., Mills, J., Poynter, D., Tyers, M. B. Nature (in the press). Feldman, S. A., Tyrrell, M. F. Br. J. Anœsth. 1970, 42, 91. Tyrrell, M. F. Anœsthesia, 1969, 24, 626. Norman, J., Katz, R. L., Seed, R. F. Br. J. Anœsth. 1970, 42, 702. Ali, H. H., Utting, J. E., Gray, C. ibid. p. 967. Savege, T. M., Blogg, C. E., Strunin, L., Simpson, B. R. Unpub-
lished. 12. Dinnick, O. P.
Anœsthesia, 1964, 19, 536.
joint involvement is unexplained and, even more puzzlingly, varies from continent to continent.7 Joint degeneration does follow trauma, congenital deformity, infection, and joint incongruity or frank cartilage destruction from other causes. It has been suggested that subtle and not easily recognisable changes of this nature are the cause of all the so-called idiopathic cases.8 Except in a few clearly syndromal forms, chemical, enzymatic, and hereditary causes have been ruled out, although clearly the later stages of osteoarthritic involvement are marked by significant metabolic changes in the articular cartilage and synovium.9 The incidence of osteoarthritis increases with There are clearly activity-related specific joint degenerations: pneumatic drill operators get arthritis of elbows and shoulders but not of fingers or wrists 1-3 ; farmers have an increased incidence of arthritis of the hip 14 ; soccer players have severe arthritis in their feet, ankles, and knees 15 ; ballet dancers have trouble with their feet.16,17 But not all high-stress activities produce joint changes. The high divers of Acapulco have no degenerative disease of the spine even though they plunge into the water from heights of over 100 feet almost daily.18 There are racial differences. Orientals have arthritis of their knees but not of their hips, whereas in Eurasians the hips and knees are equally involved.’7 And obesity plays an inconsistent role, for fat people have arthritis of the knees preferentially, but not of the hips.19 The study of the physiology of normal joint activity leads to three observations which have extremely important clinical significance:
age. 10-12
(1) the relatively high stresses applied to joints will almost always be of an impulsive nature. Walking, running, getting into or out of a chair, climbing, lifting, hammering, shovelling-all load the joints in a repetitive intermittent fashion. (Most of the force across a joint is the major product of muscular contraction and not weight-bearing. The joints of the upper extremities are therefore probably subjected to stresses-force per unit area-similar to those of the lower-extremity joints.) (2) Although rubbing back and forth does not create significant stresses across the joint, longitudinal loading does.20 The lubrication mechanisms functioning in the joint are so superb that it is difficult to conceive of the stresses of oscillation, even under extremely heavy loads, destroying the tissues. (3) In the handling of longitudinally applied forces, especially the ones of high magnitude, which by definition must be brief in intensity or else the bone will break, the cartilage and synovial fluid plays almost no role in shock absorption. It is the bone and soft tissues which attenuate these peak dynamic forces. 21
Therefore, if the joint is to wear out, one should predict that it will wear out from repetitive impulsive loading and that changes in the bone or soft tissue, which might render them less effective as shockabsorbers, would have an extremely deleterious effect on the articular cartilage. Assuming that, if degenerative arthritis was a disease of soft tissues, the manifestations of such an involvement would have presented themselves in some systemic way, one might more profitably look at alterations in the bone, especially the subchondral bone which supports the
520
joint structure.*This was done in patients manifesting the earliest phases of the disease process histochemically in their cartilage, and it was found that indeed their subchondral bone was stiffer than normal. 22 Severe degenerative joint disease has been caused in laboratory animals by repetitive impulsive loading creating bone changes similar to those seen in the patients.23 These studies were initially criticised because of their unphysiological rate of impaction (1500 c.p.m.) and their use of skeletally immature although physiologically adult animals (guineapigs). The experiments have been repeated using skeletally mature rabbits, impacted at a rate in keeping with the normal gait frequency (60 c.p.m.), with the consistent production of joint degeneration.24 The surprising thing about these experiments was the rapidity with which the full-blown disease process manifested itself after what could be considered mild-to-moderate mechanical insults. What could cause the bone to change ? Studies of the subchondral bone by thick-section micrography have demonstrated trabecular microfractures in the subchondral bone of animals subjected to repetitive impulsive loading. The increased stiffness of such bone has been correlated with the healing of these microfractures.24 Evidence of healing or healed trabecular microfractures have also been found to be preferentially present in the subchondral bone of patients with relatively early joint degeneration. 25 We know that the internal architecture of the bone is a map of the stress distributions the bone is subjected to. This response of the internal structure of bone to function is referred to as Wolff’s law and dates from the 19th century. 26B It is quite probable that such changes may well be mediated through trabecular microfracture. Therefore, in osteoarthritis, it is conceivable that we can be witnessing the natural outcome of the biological response of bone to repeated impulse loadings. The hypothetical mechanism is as follows: IMPULSE LOADING
TRABECULAR MICRO FRACTURE
1 1
BONE REMODELLING
RESULTANT STIFFENING OF BONE
INCREASED STRESS ON ARTICULAR CARTILAGE
1
CARTILAGE BREAKDOWN
JOINT
DEGENERATION
* The concept that subchondral bone can act as an effective shock absorber is not new. It was established by Dr. Physick in 1827 that a ball made of cancellous bone absorbs the energy applied to it, as contrasted with an ivory ball.
We suggest that, when the joint is subjected to repetitive impulsive loading, the bone underlying the joints, especially in the well-vascularised subchondral area, responds by remodelling its internal architecture to better resist these stresses, as one might expect from Wolff’s law. Sclerosis of the subchondral bone is an early radiological sign of osteoarthritic involvement .27 This stiffer bone is no longer as effective a shock-absorber as it was before. The articular cartilage is now relatively unprotected and the peak dynamic forces it is subjected to are increased. The first indication that anything is wrong is the loss of mucopolysaccharides from the surface layers of the cartilage, perhaps secondary to mechanical degradation, mediated lysosomally.28 The chondrocytes attempt to meet this challenge by increasing production of mucopolysaccharide, and the actual number of cells increases as well. If the increased stress persists, there is a significant loss of mucopolysaccharide, with a resultant decrease in the tissue’s mechanical integrity 29 and in its effectiveness as a bearing surface. At this point the frictional forces go up, adding to the destructive elements at work on the cartilage. Lipping and spurring are probably attempts to build out the bony framework upon which the joint rests in order to spread out the load and try to lower the load per unit area. These attempts at their repair are usually unsuccessful and progress instead to gross deformity and joint destruction. There is evidence for much of the above. Certainly the cartilage changes which occur after increased stress have been clearly defined and the progression of the joint from early to total destruction has been well documented.3OThe remodelling of subchondral bone has been shown to be a constant, active process." Remodelling through the mechanism of the healing of trabecular microfractures would seem logical and physiologically possible25 Attempts to better understand the bone’s response and the part played by vascular changes are currently under way. It has been suggested that active muscle contracture absorbs a great deal of the shock transmitted to the skeletal system. Perhaps widespread mild neuromuscular incoordination, related to cerebral vascular insufficiency, could lead to generalised osteoarthritis. It is not inconceivable that such changes retard the body’s ability to protect articular cartilage from impact loading. The sparing of the joints in a paralysed extremity from further degeneration 32" is also compatible with the "impulse loading" hypothesis, as such total paralysis severely reduces the intra-articular stresses. The epidemiology of osteoarthritis, as well as the pattern of joint involvement, are in keeping with the " impulse loading " xtiological concept. Repetitious impact loading from pneumatic drills creates degeneration of elbows and shoulders, the joints which absorb the pounding, and not the fingers or the wrists, which are just vibrated. Vibrations from riveting guns and chain-saws cause loss of body substance and peripheral neuritis but not joint degeneration. 33Patients with severe osteoporosis rarely develop degenerative arthritis. 34Osteoporotic bone would be relatively soft and would act as an excellent shock-absorber,
521
easily sustaining compression fracture of its relatively weak structure. The osteoporotic bone simply lacks the mass, even in the presence, of numerous micro and macrofractures to stiffen sufficiently and lose its protective shockabsorbing role vis-a-vis the overlying cartilage. Fracture is a very effective means of absorbing energy. The Acapulco divers have no degenerative arthritis of their cervical spines." These men were divided into two groups: those who broke the impact of the water with the top of their heads; and those who broke the impact of the water with their hands in front of their heads. The cervical spines of those whose hands break the dive had normal-appearing cervical spines on X-ray. The other group had multiple fractures, which implies that the force with which they hit the water was so great that it just broke the bone, sparing the articular surfaces of the cervical spine from what must have been very high compressive
stresses.
The distribution of joint involvement in osteoarthritis can be related to the stress applied to the joint. Stress is the force per unit area. A joint that is able to maintain a large contact area relative to its load would be less likely to develop arthritis. The ankle would be expected to rarely show degenerative changes: it is really an integral part of the series of joints that include the hind-foot and act as a universal
bearing. 35 The knee is frequently involved in meniscalrelated trauma and in obese individuals. The menisci act as washers and permit translation of the joint from a hinge to a rotational bearing. 3Once damaged, menisci act as any torn washer, and score their adjacent bearing surfaces. Fat people have trouble getting their knees together because of the girth of their thighs. As it is natural to attempt to get the feet under the centre of gravity, they walk slightly bow-legged. This diminishes the effective load-bearing area of the knee-joint, transferring it considerably medially; and we do indeed see preferential arthritic involvement of the medial side of the knee-joints in patients who are obese. 87 The hip-joint is probably the most thoroughly studied in attempts to understand degenerative joint disease. It is difficult to argue with the careful studies showing that slight incongruities do exist in some patients who go on to have degenerative hips.8 It has also been argued that ageing joints become more congruous 38 and thus less flexible under load. This may indeed have some basis of fact in a ball-andsocket joint. Recent evidence suggests that there is considerable geometrical change in both the acetabulum and the femoral head upon loading, the acetabulum spreading and the femoral head narrowing. Most of this deformation takes place in the cancellous bone.39 Thus since the joint realigns itself under load, its congruity in the older individual would be related to the relative stiffness of the subchondral bone, which might well be stiffer as the result of impact-loading through the years. The almost total absence of degenerative hip disease in Oriental populations suggests that in these populations the use of the hip is somewhat different from that in the Eurasian. If the differences were on the
basis of nutritional or constitutional differences, one might expect the absence of the disease in all joints of Orientals. In fact, the sitting and walking patterns of Orientals are quite different from those of Caucasians, and it is conceivable that the hip-joints in Orientals are subjected to considerably less repetitive impulsive loading than those of Europeans and Americans. The joints in the upper extremity which are most frequently involved in degenerative processes are the finger-joints, especially the distal ones.40 A biomechanical analysis of hand function shows that these joints are subjected to the higher stresses, especially in "feminine" forms of grasp. 41" The female preponderance of this disease could conceivably be explained on the basis of hand use, although a strongcase has been made for heredity. 40 In male populations degenerative arthritis of the hands is uncommon except following traumatic loss of congruity of these joints, and in the masculine power-grip the stress is much more evenly distributed on the finger-joints. Women who do heavy masculine work have a much lower incidence of degenerative joint changes in the hand 42 ; and in right-handed people joint changes, when they do occur, are much more severe in the right hand.43 The hypothesis that degenerative arthritis is caused
by repetitive impulsive loading appears consistent with all that has been observed so far. The importance of the subchondral bone in maintaining the integrity of the articular cartilage is a concept which makes good sense. Possibly, the reason it has taken us so long to understand osteoarthritis is that it was not until very recently that we have begun to understand joint function and in what ways the joint can fail. One looks forward to the development of a whole new armamentarium of therapeutic measures based on a more complete understanding of the disease mechanism. Requests for reprints should be addressed to E. L. R., Orthopedic Research Laboratories, Children’s Hospital Medical Center, 300 Longwood Avenue, Boston, Mass. 02115. REFERENCES
Mankin, H. J. J. Bone Jt Surg. 1970, 52A, 424. Sokoloff, L. Fedn Proc. 1966, 25, 1089. Byers, P. D., Contepomi, C. A., Farkes, T. A. Ann. rheum. Dis. 1970, 29, 15. 4. Putschar, W. Entnicklung, Wachstum und Pathologie der Beckenverbindungen des Menschen. Jena, 1931. 5. Radin, E. L., Paul, I. L., Pollock, D. Nature, 1970, 226, 554. 6. Kellgren, J. H., Lawrence, L. S. Ann. rheum. Dis. 1958, 17, 388. 7. Hoaglund, F. T., Arthur, C. M. C., Wong, W. L. Orthop. Clin. N. Am. (in the press). 8. Murray, R. O. Br. J. Radiol. 1965, 38, 810. 9. Sokoloff, L. The Biology of Degenerative Joint Disease. Chicago, 1. 2. 3.
1969. 10. 11. 12. 13.
Kellgren, J. H., Lawrence, J. S., Aitken-Swan, J. Ann. rheum. Dis. 1953, 12, 5. Brown, R., Lingg, C. Arthritis Rheum. 1961, 4, 283. Kellgren, J. H. Br. med. J. 1961, ii, 1. Hunter, D. A., McLaughlin, A. I. G., Perry, K. M. A. Br. J. industr.
Med. 1945, 2, 12. 14. Louyot, P., Savin, R. Revue Rheum. 1966, 33, 625. 15. Solonen, K. A. Annls Chir. Gynœc. Fenn. 1966, 55, 176. 16. Brodelius, A. Acta orthop. scand. 1961, 30, 309. 17. Nikolaev, I. A., Najdenov, S. Archs Mal. prof. Méd. trav. 1970, 31, 39. 18. Schneider, R. C., Papo, M., Alvarez, C. S. J. Bone Jt Surg. 1962,
44A, 648. Lawrence, J. S., Bremner, J. M., Bier, F. Ann. rheum. Dis. 1966, 25, 1. 20. Radin, E. L., Paul, I. L. Arthritis Rheum. 1971, 14, 356. 19.
522
Management and Treatment of Tropical Diseases
Reviews of Books Mayo Clinic Laboratory Manual of Hemostasis E.
J. WALTER BoWIE,
B.M., M.S., F.A.C.P., associate of medicine and clinical pathology; JOHN H. THOMPSON, JR., PH.D., associate professor of clinical pathology ; PAUL DIDISHEIM, M.D., associate professor of clinical pathology; and CHARLES A. OWEN, JR., M.D., PH.D., D.SC., F.A.c.p., professor of medicine (medical research), Mayo Graduate School of Medicine, University of Minnesota, Rochester, Minnesota. Philadelphia and London: W. B. Saunders. 1971. Pp. 186. E2.55;$6.
professor
THIS book was developed from a course given under the auspices of the American Society of Clinical Pathology. It is predominantly a practical handbook, but it starts off with very clear account of views on various aspects of haemostasis and makes good use of diagrams and tables to show how platelet function, coagulation factors, and fibrinolysis fit together. The practical instructions do not make much use of machines such as coagulometers because the authors consider them still too complex and liable to pose " maintenance problems ". Nevertheless, a method for using the Coulter counter for counting platelets is given, together with a method using the phase-contrast microscope, and they use a platelet aggregometer of their own devising for measuring platelet aggregation. For obtaining plasma for test purposes they recommend use of the Fenwal transfer-pack system. The tests they give are mostly standard and unexceptionable; they say that they have only given those tests needed for routine use. But, as might be expected from the Mayo Clinic, the list of tests is remarkably comprehensive. They include estimates of all the clotting factors and methods for assaying inhibitors of factors vmx and ix, methods for assessing platelet aggregation and platelet " retention ", and a group of methods for estimating fibrinolysis and fibrin-split products. Appendices give full details of the reagents used, with references to American sources of supply. This will be a useful handbook, especially for heematology technicians. a
Radin, E. L., Paul, I. L. ibid. 1970, 13, 139. Radin, E. L., Paul, I. L., Tolkoff, M. J. ibid. p. 400. Simon, S. R., Radin, E. L., Paul, I. L. J. Biomech. (in the press). Radin, E. L., Steinberg, R. S., Parker, H. G., et al. Meeting of the American Academy of Orthopedic Surgeons, Washington, D.C., January, 1972. 25. Pugh, J. W., Rose, R. M., Radin, E. L. Unpublished. 26. Wolff, J. Virchows Arch. 1870, 50, 389. 27. Pauwels, F. in Postgraduate Course, 9th Congress, Société Internationale de Chirurgie et Orthopédique et de Traumatologie (edited by W. P. Blount); vol. II, E-30. Vienna, 1963. 28. Bollet, A. J. Advanc. intern. Med. 1967, 13, 33. 29. Hirsch, C. Acta chir. scand. 1944, 90, suppl. 83. 30. Collins, D. H. The Pathology of Articular and Spinal Disease. London, 1949. 31. Johnson, L. C. Lab. Invest. 1956, 8, 1223. 32. Stecher, R. M., Karnosh, L. J. Am. J. med. Sci. 1947, 213, 181. 33. Horvath, F., Kakosy, T., Vollany, G. Magy. Radiol. 1969, 21, 257. 34. Smith, R. W., Rizek, J. Clin. Orthoped. 1966, 45, 31. 35. Wright, D. C., Desai, M. E., Henderson, B. S. J. Bone Jt Surg. 1964, 46A, 361. 36. Parsons, F. C. J. Anat. Physiol. Lond. 1900, 34, 301. 37. Maquet, P. Biomechanics and osteoarthritis of the knee. Congr. Soc. int. Chir Orthop. Traumat. Mexico City, 1969, p. 317. 38. Bullough, P., Goodfellow, J., Greenwald, A. S., et al. Nature, 1968, 217, 1290. 39. Mital, M. Master’s thesis, Department of Bioengineering, University of Strathclyde, Glasgow, 1970. 40. Stecher, R. M. Ann. rheum. Dis. 1955, 14, 1. 41. Radin, E. L., Parker, H. G. Lancet, 1971, i, 377. 42. Engel, A., Burch, T. A. Osteoarthritis in Adults by Selected Demographic Characteristics. Public Health Service Publication 1000, Series 11, no. 20. Washington, D.C., 1966. 43. Acheson, R. M., Chan, Y. K., Clemett, A. R. Ann. rheum. Dis. 21. 22. 23. 24.
1970, 29, 275.
by B. G. MAEGRAITH and H. M. GILLES, School of Tropical Medicine, Liverpool. Oxford: Blackwell Scientific Publications. 1971. Pp. 786. E7.50. Edited
THIS is a very full guide to the subject consisting of 59 sections on various diseases contributed by 44 authors. There are also appendices on drug dosage for children,
tropical neuropathies, antimalarial drugs, and pharmacology. The arrangement is in alphabetical order of the subjects, and this facilitates reference but makes consecutive study of groups of disorders difficult. The standard is high and the information is generally reliable and up to date; there are, however, many expressions of personal opinion, and not all the recommendations would receive universal approval or acceptance. In some sections, too, discussion of management is diluted with basic but sketchy descriptions of disease that seem to be out of place in a book which should be used in conjunction with a standard textbook if an adequate understanding of the disease being managed is to be gained. What is the place of a book like this ? The editors’ expressed aim is to provide a text for the physician practising in the tropics and other areas of the developing world to help him deal with the clinical and social problems of therapy and management. These problems cannot be considered in isolation from the rest of developing knowledge of disease, and to this extent the book is only a partial guide. It will, however, be welcomed, for it greatly augments existing texts and the information it contains will help large numbers of doctors in those parts of the tropics where knowledge of up-to-date management is
difficult trends becomes
Principles
to a
obtain and where isolation from
current
problem.
of Pathobiology
Edited by MARiANO F. LAVIA and ROLLA B. HILL, JR. London and New York: Oxford University Press. 1971.
Pp.
281.
S3.25,$7.95.
PATHOBIOLOGY is an uncomfortably hybrid title for this uncomfortably hybrid book. The first few pages carry great promise: the text will deal with " the interface between biology and pathology ", and the central theme will be " alterations in biological mechanisms that occur in response to injury ". Unfortunately, the six topics selected by the editors are not all suited to this kind of approach, and there seems to be little agreement on the level at which each contributor should write. The chapter on cell injury and cell death gives a detailed account of subcellular pathology and comes closest to fulfilling the original aim of the book. (It is also likely to cause the greatest trouble to the " busy students " at whom this text is directed.) The other chapters are broad accounts of basic processes such as inflammation, interaction between host and parasite, and immunological injury. They contribute little that is new or revealing, and several general textbooks discuss these subjects more clearly. A brave effort is made to dispatch neoplasia in 40 pages, even though the aim of the book would surely lead one to expect such an account to be concentrated on events at cellular and subcellular levels. Each chapter carries a bibliography, which varies considerably in appositeness and scope. The text is well illustrated (though there is an annoying absence of magnifications); the index is inadequate. A Practice of Anaesthesia (3rd ed. London: LloydLuke. 1972. Pp. 1549. C12).-In the third edition of their authoritative text Dr. Wylie and Dr. ChurchillDavidson have taken account of advances in anaesthesia in the past five years, and they call on five new contributors. Among topics now warranting chapters of their own are special-care units, pain in labour, and dental surgery, and there are appendices on computers and statistics.
of
Hypothesis ROLE OF MECHANICAL FACTORS IN PATHOGENESIS OF PRIMARY OSTEOARTHRITIS IGOR L. PAUL ERIC L. RADIN ROBERT M. ROSE Research Laboratories, Harvard Medical School, Orthopedic Children’s Hospital Medical Center, Boston, Massachusetts 02115, and Department of Mechanical Engineering and Department of Metallurgy and Materials Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
Studies of the relation between joint function and mechanical stress have led to a revival of the old concept that primary osteoarthritis is actually a wearing out of joints. Recent experimental evidence suggests that joints can wear out by repetitive impulsive loading, rather than by rubbing. This new mechanistic approach is compatible with the pathology of, and clinical experience with, the disease.
Sum ary
THE concept that osteoarthritis is simply a wearing of joints, a natural ageing and attrition of Nature’s bearings subjected to years of long and hard use, has almost completely fallen from favour over the past two decades. Articular cartilage has been shown in the adult to be an active and viable tissue quite capable of producing excessive amounts of mucoout
1
polysaccharide and collagen in response to injury. Adult articular cartilage in and of itself does not mechanically change with age.2 The attrition of articular cartilage in areas systematically deprived of load-bearing has been shown to be unrelated to the development of joint degeneration,3,4 and it has been found that joints move even under high loads with amazingly low coefficients of friction, rendering almost completely untenable the possibility that joints wear
5 away from back-and-forth motion.5
Observa-
limited to clinical experience, demonstrates time and again individuals who have done hard work all their lives without manifestations of joint degeneration. The disease has a predilection for womenwho in general seem to subject their joints to much less stress. Furthermore, the pattern
tion, certainly
1. 2. 3.
4. 5. 6. 7. 8. 9. 10. 11.
not
Bourne, J. G., Collier, H. O. J., Somers, C. F. Lancet, 1952, i, 1225. Roth, F., Wüthrick, H. Br. J. Anœsth. 1969, 41, 311. Mathias, J. A., Evans Prosser, C. D. G. Prog. Anœsth. 1970, p. 1153. Kelman, G. R., Kennedy, R. R. Br. J. Anœsth. 1971, 43, 335. Strunin, L., Strunin, J. M., Layton, J., Sim, A. W., Simpson, B. R. Unpublished. Bolger, L., Brittain, R. T., Jack, D., Jackson, M. R., Martin, L. E., Mills, J., Poynter, D., Tyers, M. B. Nature (in the press). Feldman, S. A., Tyrrell, M. F. Br. J. Anœsth. 1970, 42, 91. Tyrrell, M. F. Anœsthesia, 1969, 24, 626. Norman, J., Katz, R. L., Seed, R. F. Br. J. Anœsth. 1970, 42, 702. Ali, H. H., Utting, J. E., Gray, C. ibid. p. 967. Savege, T. M., Blogg, C. E., Strunin, L., Simpson, B. R. Unpub-
lished. 12. Dinnick, O. P.
Anœsthesia, 1964, 19, 536.
joint involvement is unexplained and, even more puzzlingly, varies from continent to continent.7 Joint degeneration does follow trauma, congenital deformity, infection, and joint incongruity or frank cartilage destruction from other causes. It has been suggested that subtle and not easily recognisable changes of this nature are the cause of all the so-called idiopathic cases.8 Except in a few clearly syndromal forms, chemical, enzymatic, and hereditary causes have been ruled out, although clearly the later stages of osteoarthritic involvement are marked by significant metabolic changes in the articular cartilage and synovium.9 The incidence of osteoarthritis increases with There are clearly activity-related specific joint degenerations: pneumatic drill operators get arthritis of elbows and shoulders but not of fingers or wrists 1-3 ; farmers have an increased incidence of arthritis of the hip 14 ; soccer players have severe arthritis in their feet, ankles, and knees 15 ; ballet dancers have trouble with their feet.16,17 But not all high-stress activities produce joint changes. The high divers of Acapulco have no degenerative disease of the spine even though they plunge into the water from heights of over 100 feet almost daily.18 There are racial differences. Orientals have arthritis of their knees but not of their hips, whereas in Eurasians the hips and knees are equally involved.’7 And obesity plays an inconsistent role, for fat people have arthritis of the knees preferentially, but not of the hips.19 The study of the physiology of normal joint activity leads to three observations which have extremely important clinical significance:
age. 10-12
(1) the relatively high stresses applied to joints will almost always be of an impulsive nature. Walking, running, getting into or out of a chair, climbing, lifting, hammering, shovelling-all load the joints in a repetitive intermittent fashion. (Most of the force across a joint is the major product of muscular contraction and not weight-bearing. The joints of the upper extremities are therefore probably subjected to stresses-force per unit area-similar to those of the lower-extremity joints.) (2) Although rubbing back and forth does not create significant stresses across the joint, longitudinal loading does.20 The lubrication mechanisms functioning in the joint are so superb that it is difficult to conceive of the stresses of oscillation, even under extremely heavy loads, destroying the tissues. (3) In the handling of longitudinally applied forces, especially the ones of high magnitude, which by definition must be brief in intensity or else the bone will break, the cartilage and synovial fluid plays almost no role in shock absorption. It is the bone and soft tissues which attenuate these peak dynamic forces. 21
Therefore, if the joint is to wear out, one should predict that it will wear out from repetitive impulsive loading and that changes in the bone or soft tissue, which might render them less effective as shockabsorbers, would have an extremely deleterious effect on the articular cartilage. Assuming that, if degenerative arthritis was a disease of soft tissues, the manifestations of such an involvement would have presented themselves in some systemic way, one might more profitably look at alterations in the bone, especially the subchondral bone which supports the
520
joint structure.*This was done in patients manifesting the earliest phases of the disease process histochemically in their cartilage, and it was found that indeed their subchondral bone was stiffer than normal. 22 Severe degenerative joint disease has been caused in laboratory animals by repetitive impulsive loading creating bone changes similar to those seen in the patients.23 These studies were initially criticised because of their unphysiological rate of impaction (1500 c.p.m.) and their use of skeletally immature although physiologically adult animals (guineapigs). The experiments have been repeated using skeletally mature rabbits, impacted at a rate in keeping with the normal gait frequency (60 c.p.m.), with the consistent production of joint degeneration.24 The surprising thing about these experiments was the rapidity with which the full-blown disease process manifested itself after what could be considered mild-to-moderate mechanical insults. What could cause the bone to change ? Studies of the subchondral bone by thick-section micrography have demonstrated trabecular microfractures in the subchondral bone of animals subjected to repetitive impulsive loading. The increased stiffness of such bone has been correlated with the healing of these microfractures.24 Evidence of healing or healed trabecular microfractures have also been found to be preferentially present in the subchondral bone of patients with relatively early joint degeneration. 25 We know that the internal architecture of the bone is a map of the stress distributions the bone is subjected to. This response of the internal structure of bone to function is referred to as Wolff’s law and dates from the 19th century. 26B It is quite probable that such changes may well be mediated through trabecular microfracture. Therefore, in osteoarthritis, it is conceivable that we can be witnessing the natural outcome of the biological response of bone to repeated impulse loadings. The hypothetical mechanism is as follows: IMPULSE LOADING
TRABECULAR MICRO FRACTURE
1 1
BONE REMODELLING
RESULTANT STIFFENING OF BONE
INCREASED STRESS ON ARTICULAR CARTILAGE
1
CARTILAGE BREAKDOWN
JOINT
DEGENERATION
* The concept that subchondral bone can act as an effective shock absorber is not new. It was established by Dr. Physick in 1827 that a ball made of cancellous bone absorbs the energy applied to it, as contrasted with an ivory ball.
We suggest that, when the joint is subjected to repetitive impulsive loading, the bone underlying the joints, especially in the well-vascularised subchondral area, responds by remodelling its internal architecture to better resist these stresses, as one might expect from Wolff’s law. Sclerosis of the subchondral bone is an early radiological sign of osteoarthritic involvement .27 This stiffer bone is no longer as effective a shock-absorber as it was before. The articular cartilage is now relatively unprotected and the peak dynamic forces it is subjected to are increased. The first indication that anything is wrong is the loss of mucopolysaccharides from the surface layers of the cartilage, perhaps secondary to mechanical degradation, mediated lysosomally.28 The chondrocytes attempt to meet this challenge by increasing production of mucopolysaccharide, and the actual number of cells increases as well. If the increased stress persists, there is a significant loss of mucopolysaccharide, with a resultant decrease in the tissue’s mechanical integrity 29 and in its effectiveness as a bearing surface. At this point the frictional forces go up, adding to the destructive elements at work on the cartilage. Lipping and spurring are probably attempts to build out the bony framework upon which the joint rests in order to spread out the load and try to lower the load per unit area. These attempts at their repair are usually unsuccessful and progress instead to gross deformity and joint destruction. There is evidence for much of the above. Certainly the cartilage changes which occur after increased stress have been clearly defined and the progression of the joint from early to total destruction has been well documented.3OThe remodelling of subchondral bone has been shown to be a constant, active process." Remodelling through the mechanism of the healing of trabecular microfractures would seem logical and physiologically possible25 Attempts to better understand the bone’s response and the part played by vascular changes are currently under way. It has been suggested that active muscle contracture absorbs a great deal of the shock transmitted to the skeletal system. Perhaps widespread mild neuromuscular incoordination, related to cerebral vascular insufficiency, could lead to generalised osteoarthritis. It is not inconceivable that such changes retard the body’s ability to protect articular cartilage from impact loading. The sparing of the joints in a paralysed extremity from further degeneration 32" is also compatible with the "impulse loading" hypothesis, as such total paralysis severely reduces the intra-articular stresses. The epidemiology of osteoarthritis, as well as the pattern of joint involvement, are in keeping with the " impulse loading " xtiological concept. Repetitious impact loading from pneumatic drills creates degeneration of elbows and shoulders, the joints which absorb the pounding, and not the fingers or the wrists, which are just vibrated. Vibrations from riveting guns and chain-saws cause loss of body substance and peripheral neuritis but not joint degeneration. 33Patients with severe osteoporosis rarely develop degenerative arthritis. 34Osteoporotic bone would be relatively soft and would act as an excellent shock-absorber,
521
easily sustaining compression fracture of its relatively weak structure. The osteoporotic bone simply lacks the mass, even in the presence, of numerous micro and macrofractures to stiffen sufficiently and lose its protective shockabsorbing role vis-a-vis the overlying cartilage. Fracture is a very effective means of absorbing energy. The Acapulco divers have no degenerative arthritis of their cervical spines." These men were divided into two groups: those who broke the impact of the water with the top of their heads; and those who broke the impact of the water with their hands in front of their heads. The cervical spines of those whose hands break the dive had normal-appearing cervical spines on X-ray. The other group had multiple fractures, which implies that the force with which they hit the water was so great that it just broke the bone, sparing the articular surfaces of the cervical spine from what must have been very high compressive
stresses.
The distribution of joint involvement in osteoarthritis can be related to the stress applied to the joint. Stress is the force per unit area. A joint that is able to maintain a large contact area relative to its load would be less likely to develop arthritis. The ankle would be expected to rarely show degenerative changes: it is really an integral part of the series of joints that include the hind-foot and act as a universal
bearing. 35 The knee is frequently involved in meniscalrelated trauma and in obese individuals. The menisci act as washers and permit translation of the joint from a hinge to a rotational bearing. 3Once damaged, menisci act as any torn washer, and score their adjacent bearing surfaces. Fat people have trouble getting their knees together because of the girth of their thighs. As it is natural to attempt to get the feet under the centre of gravity, they walk slightly bow-legged. This diminishes the effective load-bearing area of the knee-joint, transferring it considerably medially; and we do indeed see preferential arthritic involvement of the medial side of the knee-joints in patients who are obese. 87 The hip-joint is probably the most thoroughly studied in attempts to understand degenerative joint disease. It is difficult to argue with the careful studies showing that slight incongruities do exist in some patients who go on to have degenerative hips.8 It has also been argued that ageing joints become more congruous 38 and thus less flexible under load. This may indeed have some basis of fact in a ball-andsocket joint. Recent evidence suggests that there is considerable geometrical change in both the acetabulum and the femoral head upon loading, the acetabulum spreading and the femoral head narrowing. Most of this deformation takes place in the cancellous bone.39 Thus since the joint realigns itself under load, its congruity in the older individual would be related to the relative stiffness of the subchondral bone, which might well be stiffer as the result of impact-loading through the years. The almost total absence of degenerative hip disease in Oriental populations suggests that in these populations the use of the hip is somewhat different from that in the Eurasian. If the differences were on the
basis of nutritional or constitutional differences, one might expect the absence of the disease in all joints of Orientals. In fact, the sitting and walking patterns of Orientals are quite different from those of Caucasians, and it is conceivable that the hip-joints in Orientals are subjected to considerably less repetitive impulsive loading than those of Europeans and Americans. The joints in the upper extremity which are most frequently involved in degenerative processes are the finger-joints, especially the distal ones.40 A biomechanical analysis of hand function shows that these joints are subjected to the higher stresses, especially in "feminine" forms of grasp. 41" The female preponderance of this disease could conceivably be explained on the basis of hand use, although a strongcase has been made for heredity. 40 In male populations degenerative arthritis of the hands is uncommon except following traumatic loss of congruity of these joints, and in the masculine power-grip the stress is much more evenly distributed on the finger-joints. Women who do heavy masculine work have a much lower incidence of degenerative joint changes in the hand 42 ; and in right-handed people joint changes, when they do occur, are much more severe in the right hand.43 The hypothesis that degenerative arthritis is caused
by repetitive impulsive loading appears consistent with all that has been observed so far. The importance of the subchondral bone in maintaining the integrity of the articular cartilage is a concept which makes good sense. Possibly, the reason it has taken us so long to understand osteoarthritis is that it was not until very recently that we have begun to understand joint function and in what ways the joint can fail. One looks forward to the development of a whole new armamentarium of therapeutic measures based on a more complete understanding of the disease mechanism. Requests for reprints should be addressed to E. L. R., Orthopedic Research Laboratories, Children’s Hospital Medical Center, 300 Longwood Avenue, Boston, Mass. 02115. REFERENCES
Mankin, H. J. J. Bone Jt Surg. 1970, 52A, 424. Sokoloff, L. Fedn Proc. 1966, 25, 1089. Byers, P. D., Contepomi, C. A., Farkes, T. A. Ann. rheum. Dis. 1970, 29, 15. 4. Putschar, W. Entnicklung, Wachstum und Pathologie der Beckenverbindungen des Menschen. Jena, 1931. 5. Radin, E. L., Paul, I. L., Pollock, D. Nature, 1970, 226, 554. 6. Kellgren, J. H., Lawrence, L. S. Ann. rheum. Dis. 1958, 17, 388. 7. Hoaglund, F. T., Arthur, C. M. C., Wong, W. L. Orthop. Clin. N. Am. (in the press). 8. Murray, R. O. Br. J. Radiol. 1965, 38, 810. 9. Sokoloff, L. The Biology of Degenerative Joint Disease. Chicago, 1. 2. 3.
1969. 10. 11. 12. 13.
Kellgren, J. H., Lawrence, J. S., Aitken-Swan, J. Ann. rheum. Dis. 1953, 12, 5. Brown, R., Lingg, C. Arthritis Rheum. 1961, 4, 283. Kellgren, J. H. Br. med. J. 1961, ii, 1. Hunter, D. A., McLaughlin, A. I. G., Perry, K. M. A. Br. J. industr.
Med. 1945, 2, 12. 14. Louyot, P., Savin, R. Revue Rheum. 1966, 33, 625. 15. Solonen, K. A. Annls Chir. Gynœc. Fenn. 1966, 55, 176. 16. Brodelius, A. Acta orthop. scand. 1961, 30, 309. 17. Nikolaev, I. A., Najdenov, S. Archs Mal. prof. Méd. trav. 1970, 31, 39. 18. Schneider, R. C., Papo, M., Alvarez, C. S. J. Bone Jt Surg. 1962,
44A, 648. Lawrence, J. S., Bremner, J. M., Bier, F. Ann. rheum. Dis. 1966, 25, 1. 20. Radin, E. L., Paul, I. L. Arthritis Rheum. 1971, 14, 356. 19.
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Management and Treatment of Tropical Diseases
Reviews of Books Mayo Clinic Laboratory Manual of Hemostasis E.
J. WALTER BoWIE,
B.M., M.S., F.A.C.P., associate of medicine and clinical pathology; JOHN H. THOMPSON, JR., PH.D., associate professor of clinical pathology ; PAUL DIDISHEIM, M.D., associate professor of clinical pathology; and CHARLES A. OWEN, JR., M.D., PH.D., D.SC., F.A.c.p., professor of medicine (medical research), Mayo Graduate School of Medicine, University of Minnesota, Rochester, Minnesota. Philadelphia and London: W. B. Saunders. 1971. Pp. 186. E2.55;$6.
professor
THIS book was developed from a course given under the auspices of the American Society of Clinical Pathology. It is predominantly a practical handbook, but it starts off with very clear account of views on various aspects of haemostasis and makes good use of diagrams and tables to show how platelet function, coagulation factors, and fibrinolysis fit together. The practical instructions do not make much use of machines such as coagulometers because the authors consider them still too complex and liable to pose " maintenance problems ". Nevertheless, a method for using the Coulter counter for counting platelets is given, together with a method using the phase-contrast microscope, and they use a platelet aggregometer of their own devising for measuring platelet aggregation. For obtaining plasma for test purposes they recommend use of the Fenwal transfer-pack system. The tests they give are mostly standard and unexceptionable; they say that they have only given those tests needed for routine use. But, as might be expected from the Mayo Clinic, the list of tests is remarkably comprehensive. They include estimates of all the clotting factors and methods for assaying inhibitors of factors vmx and ix, methods for assessing platelet aggregation and platelet " retention ", and a group of methods for estimating fibrinolysis and fibrin-split products. Appendices give full details of the reagents used, with references to American sources of supply. This will be a useful handbook, especially for heematology technicians. a
Radin, E. L., Paul, I. L. ibid. 1970, 13, 139. Radin, E. L., Paul, I. L., Tolkoff, M. J. ibid. p. 400. Simon, S. R., Radin, E. L., Paul, I. L. J. Biomech. (in the press). Radin, E. L., Steinberg, R. S., Parker, H. G., et al. Meeting of the American Academy of Orthopedic Surgeons, Washington, D.C., January, 1972. 25. Pugh, J. W., Rose, R. M., Radin, E. L. Unpublished. 26. Wolff, J. Virchows Arch. 1870, 50, 389. 27. Pauwels, F. in Postgraduate Course, 9th Congress, Société Internationale de Chirurgie et Orthopédique et de Traumatologie (edited by W. P. Blount); vol. II, E-30. Vienna, 1963. 28. Bollet, A. J. Advanc. intern. Med. 1967, 13, 33. 29. Hirsch, C. Acta chir. scand. 1944, 90, suppl. 83. 30. Collins, D. H. The Pathology of Articular and Spinal Disease. London, 1949. 31. Johnson, L. C. Lab. Invest. 1956, 8, 1223. 32. Stecher, R. M., Karnosh, L. J. Am. J. med. Sci. 1947, 213, 181. 33. Horvath, F., Kakosy, T., Vollany, G. Magy. Radiol. 1969, 21, 257. 34. Smith, R. W., Rizek, J. Clin. Orthoped. 1966, 45, 31. 35. Wright, D. C., Desai, M. E., Henderson, B. S. J. Bone Jt Surg. 1964, 46A, 361. 36. Parsons, F. C. J. Anat. Physiol. Lond. 1900, 34, 301. 37. Maquet, P. Biomechanics and osteoarthritis of the knee. Congr. Soc. int. Chir Orthop. Traumat. Mexico City, 1969, p. 317. 38. Bullough, P., Goodfellow, J., Greenwald, A. S., et al. Nature, 1968, 217, 1290. 39. Mital, M. Master’s thesis, Department of Bioengineering, University of Strathclyde, Glasgow, 1970. 40. Stecher, R. M. Ann. rheum. Dis. 1955, 14, 1. 41. Radin, E. L., Parker, H. G. Lancet, 1971, i, 377. 42. Engel, A., Burch, T. A. Osteoarthritis in Adults by Selected Demographic Characteristics. Public Health Service Publication 1000, Series 11, no. 20. Washington, D.C., 1966. 43. Acheson, R. M., Chan, Y. K., Clemett, A. R. Ann. rheum. Dis. 21. 22. 23. 24.
1970, 29, 275.
by B. G. MAEGRAITH and H. M. GILLES, School of Tropical Medicine, Liverpool. Oxford: Blackwell Scientific Publications. 1971. Pp. 786. E7.50. Edited
THIS is a very full guide to the subject consisting of 59 sections on various diseases contributed by 44 authors. There are also appendices on drug dosage for children,
tropical neuropathies, antimalarial drugs, and pharmacology. The arrangement is in alphabetical order of the subjects, and this facilitates reference but makes consecutive study of groups of disorders difficult. The standard is high and the information is generally reliable and up to date; there are, however, many expressions of personal opinion, and not all the recommendations would receive universal approval or acceptance. In some sections, too, discussion of management is diluted with basic but sketchy descriptions of disease that seem to be out of place in a book which should be used in conjunction with a standard textbook if an adequate understanding of the disease being managed is to be gained. What is the place of a book like this ? The editors’ expressed aim is to provide a text for the physician practising in the tropics and other areas of the developing world to help him deal with the clinical and social problems of therapy and management. These problems cannot be considered in isolation from the rest of developing knowledge of disease, and to this extent the book is only a partial guide. It will, however, be welcomed, for it greatly augments existing texts and the information it contains will help large numbers of doctors in those parts of the tropics where knowledge of up-to-date management is
difficult trends becomes
Principles
to a
obtain and where isolation from
current
problem.
of Pathobiology
Edited by MARiANO F. LAVIA and ROLLA B. HILL, JR. London and New York: Oxford University Press. 1971.
Pp.
281.
S3.25,$7.95.
PATHOBIOLOGY is an uncomfortably hybrid title for this uncomfortably hybrid book. The first few pages carry great promise: the text will deal with " the interface between biology and pathology ", and the central theme will be " alterations in biological mechanisms that occur in response to injury ". Unfortunately, the six topics selected by the editors are not all suited to this kind of approach, and there seems to be little agreement on the level at which each contributor should write. The chapter on cell injury and cell death gives a detailed account of subcellular pathology and comes closest to fulfilling the original aim of the book. (It is also likely to cause the greatest trouble to the " busy students " at whom this text is directed.) The other chapters are broad accounts of basic processes such as inflammation, interaction between host and parasite, and immunological injury. They contribute little that is new or revealing, and several general textbooks discuss these subjects more clearly. A brave effort is made to dispatch neoplasia in 40 pages, even though the aim of the book would surely lead one to expect such an account to be concentrated on events at cellular and subcellular levels. Each chapter carries a bibliography, which varies considerably in appositeness and scope. The text is well illustrated (though there is an annoying absence of magnifications); the index is inadequate. A Practice of Anaesthesia (3rd ed. London: LloydLuke. 1972. Pp. 1549. C12).-In the third edition of their authoritative text Dr. Wylie and Dr. ChurchillDavidson have taken account of advances in anaesthesia in the past five years, and they call on five new contributors. Among topics now warranting chapters of their own are special-care units, pain in labour, and dental surgery, and there are appendices on computers and statistics.