Rheumatology Advance Access originally published online on November 15, 2005
Rheumatology 2006 45(2):146-149; doi:10.1093/rheumatology/kei197
© The Author 2005. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Conditioning of cartilage during normal activities is an important factor in the development of osteoarthritis
B. B. Seedhom
Bioengineering Division, Academic Unit of Musculoskeletal and Rehabilitation Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
Correspondence to: B. B. Seedhom. Bioengineering Division, Academic Unit of Musculoskeletal and Rehabilitation Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK. E-mail: b.b.seedhom{at}leeds.ac.uk
 |
Abstract
|
|---|
Mechanical factors have long been implicated in the aetiology
of osteoarthritis (OA). The two most popular hypotheses regarding
the mechanism of cartilage damage are: the application of too
high a stress and the mechanism of fatigue. Mechanical failure
in any material, however, can be caused by either or both of
these mechanisms. It is hypothesized that, because cartilage
is a living tissue, the threshold at which it fails by either
mechanism is regulated by the prevalent stresses arising in
a joint. As these stresses are determined by activities and
lifestyles, a low failure threshold can be the result of prolonged
periods of low-level activity, which, if interrupted with short
periods of intense activities, can subject weakened cartilage
to damaging stresses. Were this hypothesis proven, it would
address difficulties encountered with these hypotheses and explain
some clinical observations. It would also have implications
for the activities and lifestyles of individuals.
|
Introduction
|
|---|
Factors often implicated in the development of osteoarthritis
(OA) comprise those that increase the susceptibility to the
disease (including age, sex, heredity, ethnic characteristics,
hypermobility and osteoporosis) and those which have been directly
implicated in causing mechanical damage to the articular cartilage.
Amongst these latter factors are obesity (albeit controversial)
[
1], trauma, muscle weakness, joint deformation and repetitive
use (whether occupational or leisure) [
2,
3]. These are termed
mechanical factors because they affect both the level and the
manner in which joints are loaded and the cartilage stressed.
Two major hypotheses underlie these factors: the hypothesis
of too high stress and the hypothesis of fatigue. Both of these
are discussed in this article, which is concerned with the mechanism
by which the earliest damage to cartilage is caused by mechanical
stresses arising in normal daily activities. The article is
concerned neither with damage caused by abnormally high stresses
arising in trauma nor with subsequent degeneration observed
in the natural history of the disease.
|
Mechanical failure of cartilage: review of traditional hypotheses
|
|---|
Freund [
4] proposed that there is a certain range of loading
of cartilage that is conducive to its health; above and below
this the tissues suffer. However, the view that cartilage will
be damaged when subjected to too high stresses is as true of
cartilage as it is of any biological tissue or engineering component,
and so this view is not useful beyond saying that trauma is
instrumental in damaging articular surfaces of a joint and bringing
about the disease. Further, and more importantly, it does not
define a safe upper limit for such stress for cartilage, which
raises the question of whether this upper limit can be the same
for two individuals of the same age, one active in sport and
the other sedentary, or whether it can be the same for two individuals
of similar occupations but of widely different age.
The opposite idea has also been suggested: that it is too little rather than too much stress that initiates the osteoarthritic process [5, 6]. The latter study cited the ‘odd’ medial facet of the patella where degenerative changes have been observed, but which are non-progressive and rarely advance beyond overt fibrillation [7]. This facet of the patella comes into contact with the femur at knee flexion angles above 135°, which is greatly beyond where the knee is flexed during ambulatory and most sedentary activities. The degenerative surface changes observed in this facet were thus attributed to habitual disuse, but no mechanism of how these changes occurred was described.
Fatigue was proposed as a mechanism of failure of articular cartilage [8]; this is likely to be a tensile failure of the collagen meshwork, either as a result of a single application of a large load (such as that which might occur in trauma) or of cumulative cyclic application of a lower load (such as that which occurs in normal daily activities). Later, in discussion of their hypothesis about the aetiology of OA, Freeman and Meachim [9] proposed that the increasing incidence of fibrillation with age may be accounted for by an increased rate of inception of fragmentation in the fibre network, due to diminishing fatigue strength in that network with age and the virtual absence of any capacity for repair. This view is in accordance with two studies [10, 11], both of which demonstrated that cartilage exhibits typical fatigue behaviour and showed further that fatigue resistance decreased with advancing age (Fig. 1a) (however, the correlation of fatigue fracture stress with age is somewhat tenuous; see legend of Fig. 1). Again, it is expected that cartilage, like all materials, is susceptible to fatigue failure. What is remarkable is the considerable scatter in the data; on examining the two fatigue studies, there are individuals between the ages of 20 and 60 yr with equally good and equally poor cartilage resistance to fatigue. More remarkable is the scatter in the age-related values of the tensile properties of intact cartilage in Kempson's study on the knee [12] and later on the hip and ankle [13]. For instance, in the hip [13], the tensile fracture stress of the cartilage surface layer varies between 21 and 30 MPa in the second decade, between 16 and 40 MPa in the third decade, between 16 and 31 in the fourth decade and between 12 and 27 MPa in the seventh decade. Of particular interest are the data on the ankle cartilage [13], which show not only large scatter in the data but also a much slower decline in the tensile fracture stress with age. Surprisingly, the data show a slight increase in the tensile stiffness of ankle cartilage (indicating improvement) with age. Such scatter and, more importantly, overlap of ranges of values describing cartilage properties within widely separate decades of life may not be solely attributable to normal biological variations.
View larger version (19K):
[in this window]
[in a new window]
|
FIG. 1 (a) All data from studies [10, 11] have been combined and reproduced here. On performing linear regression analysis on the data obtained at 20–75 yr (i.e. excluding points 1–5 from the analysis), the slope of the curve reduces from 0.132 to 0.096 and R2 from 0.41 to 0.22 (the linear regression of this analysis is not shown here). (b) However, if another point in the third decade (point 6) is considered an outlier and eliminated from the analysis, the correlation between fatigue resistance and age diminishes further; the slope of the regression line halves, indicating a weaker effect of age on fatigue resistance, and R2 reduces from 0.409 to 0.13, indicating a weaker significance of the correlation between age and cartilage fatigue resistance.
|
|
Below we discuss a hypothesis (which has been formulated and
tested in a series of cadaveric studies) that implicates, in
cartilage damage, an adaptive mechanism linking cartilage properties
with the mechanical stimuli to which it is exposed during normal
daily activities.
|
Mechanical conditioning of articular cartilage
|
|---|
A study [
14] undertaken on the osteoarthritic lesions that are
observed on the patello-femoral compartment of the knee joint
[
15,
16] showed that these lesions were always present where
contact occurred between the femur and patella at knee flexion
angles of between 40° and 80° (
Fig. 2). Furthermore,
the contact stresses that normally act on these areas during
ambulatory activities followed an interesting pattern, in that
during level walking (the most predominant activity of Western
man, occupying 95% or more of the time of human locomotion),
cartilage is subjected to compressive stresses of 1 MPa or even
less. In other (much less frequent) activities, such as walking
up or down a ramp and the ascent or descent of stairs, the cartilage
is subjected to much higher stresses: between 4 and 6 MPa. This
observation led to the hypothesis that cartilage (where the
lesions are observed) becomes mechanically conditioned to transmit,
without sustaining damage, that stress to which it is most regularly
subjected, and that damage would occur when cartilage is subjected
to the greater stresses that act less frequently during the
other activities. If the rate of damage were greater than that
of repair, the accumulation of minor damage, which might be
initially manifest as minimal fibrillation, would progress to
more serious degenerative changes. In other words, because cartilage
is a living tissue the stress threshold at which it will fail
is regulated by the prevalent/predominant stresses arising in
joints. As these stresses are determined by the activities and
lifestyles of individuals, the failure threshold will vary for
different individuals at any age, and also for different sites/regions
in some joints (especially complex ones such as the knee).
View larger version (22K):
[in this window]
[in a new window]
|
FIG. 2. Schematic summary of study [14], illustrating contact areas between the femur and patella (delineated and labelled) corresponding to knee flexion angles of 10°, 25°, 45°, 60°, 90°, 115° and 130°, and location of the OA lesion (area in orange) in relation to the patello-femoral contact areas throughout the range of knee flexion. As can be readily observed, the lesion occurred where the femur and patella made contact at knee flexion angles between 40° and 80°. Cartilage in this area is conditioned by the low stress (1 MPa) that acts during level walking (which represents 95% of the activity of the Western individual) and so may sustain damage when much higher but infrequent stresses (4–6 MPa) act during ramp and stair ascent/descent.
|
|
The author's group undertook three further studies on cadaveric
joints, the results of which were in harmony with the hypothesis.
These studies included surveys of the mechanical properties
of cartilage on the entire surfaces of joints. They primarily
tested the corollary/subhypothesis that if mechanical stress
conditions cartilage, it would be expected that in any synovial
joint the cartilage should be stiffer in areas that are predominantly
more highly stressed than in areas which are predominantly subjected
to low stresses. By high and low stresses are meant those arising
in normal daily activities, not in trauma. The first study [
17],
on two groups of knee and ankle joints, showed that the cartilage
from the ankle tibio-talar joint was stiffest (had the highest
compressive modulus) and that from patellar surfaces of the
femur had the lowest stiffness. On ranking the various joint
areas in descending order of cartilage stiffness (i.e. that
with the highest compressive modulus first and that with the
lowest last), the corresponding predominant stress acting on
these areas followed the same ranking order (
Table 1). Because
the cadaveric knees and ankles in that study were from different
populations and because the stresses acting on the various areas
tested were not measured directly but rather taken as those
reported in other studies, the second study [
18] was undertaken
on a group of knees and ankles from the ipsilateral side. In
this study, the stresses arising in these joints were determined
experimentally. This second study confirmed the results of the
first. The third study [
19], on ipsilateral sets of hips, knees
and ankles, confirmed the results of the previous two. The advantage
of the studies on joints from the ipsilateral side is that it
may be safely assumed that joints from the same leg were subjected
to the same number of loading cycles. These findings have been
corroborated by a recent study that demonstrated similar differences
in biomechanical properties between ankle and knee cartilage
[
20].
View this table:
[in this window]
[in a new window]
|
TABLE 1. Mechanical properties of cartilage (MN/m2) and corresponding stresses (MPa) occurring in the various areas in the knee and ankle joints (from reference [17])
|
|
The cadaveric studies [
14,
17–19] have thus confirmed
that in the three major joints of the lower limb there is a
correlation between the prevalent stresses arising during locomotion
in the different joint areas and the cartilage properties in
these areas. These studies, however, do not prove the proposed
hypothesis, but rather provide the necessary (but not sufficient)
circumstantial evidence that it might be true.
A rigorous test of the hypothesis should aim to induce, in living joints, cartilage fibrillation similar to that observed in early OA. This test would be undertaken in an animal model in which the animals would be put through controlled exercise regimens that produced in the joints the stress patterns implicated in the aetiology of OA, as the present hypothesis proposes. Four groups would be necessary. The first of these would be a control animal that is allowed to roam freely. The second would be subject to constraints reducing the level of activity and in turn the mechanical stress acting on the joints. The third would be encouraged to increase its degree of activity to increase the level of stress. By measuring the mechanical properties of cartilage in these three groups it would be possible to ascertain whether the reduction in the level of activity of the second group (below that of the first control group) had resulted in a corresponding reduction in cartilage stiffness, and that an increase in the level of activity in the third had resulted in a corresponding increase in cartilage stiffness. The fourth group would then be subjected to a regimen of alternately prolonged periods of reduced joint stress (causing deterioration in cartilage properties) and occasional short periods of strenuous exercise, inducing high stresses on the joints. It would then be possible to ascertain whether this regimen would induce fibrillated lesions in articular cartilage. This test has not yet been attempted for many reasons, the most important of which is the present climate and attitude towards animal studies.
Despite this difficulty, the following important clinical observations that are not adequately explained by the stress and fatigue hypotheses can be explained by the proposed hypothesis (were it proven true).
- In the cadaveric studies from the author's group, osteoarthritic lesions were observed in some of the knee joints—on the patellar surfaces of the femur and on the areas not covered by the menisci. These two areas are predominantly subject to low stresses, but occasionally to much higher stresses. No OA lesions were observed in the tibio-talar joints of the ankles tested. It is especially noteworthy that the tibio-talar joint in the ankle, which has the lowest incidence of OA [21–25], is also predominantly subjected to high stresses [26]. The reasons for this predominance of high stresses in the tibio-talar joint are: (a) loads of similar magnitudes to those acting on the knee act on the tibio-talar joint but are distributed on much smaller articular surfaces than those of the knee; and (b) the tibio-talar joint has a much smaller range of movement and a relatively simple and congruous geometry, which cause almost its entire surface to be stressed during locomotion.
- The increased incidence of OA in knees after meniscectomy [27, 28] can be explained as a result of the large and sudden increase in the stresses acting on the areas not covered by the menisci due to the transfer of the entire load that acts in the tibiofemoral joint onto these areas after the removal of the menisci [29, 30].
- The reported increase in incidence of OA lesions in the inferior third of the patellar surface [31] (which is loaded at the lower angles of knee flexion) in anterior-cruciate-deficient knees can be explained by increased stresses in this area as a result of altered tracking of the patella.
- The mild damage observed in the ‘odd’ facet of the patella that is not habitually stressed [6] can be the result of the infrequent application of high stress when this area comes into contact with the femur during such activities as squatting and rising up from a deep squat, which are relatively rarely practised in the West and during which large loads arise in the joint [32].
- The scatter of the cartilage properties and, in particular, the fatigue resistance observed within the various decades of life [10–13] can be explained by mechanical conditioning of cartilage as a result of the different lifestyles; more active older individuals would have stiffer/stronger and healthier cartilage with higher failure thresholds than younger sedentary individuals.
|
Implications of the hypothesis
|
|---|
In conclusion, the conditioning hypothesis proposes that degenerative
changes in cartilage that can lead to OA might be associated
with a Western lifestyle, in which many people exercise in short
sharp bursts, often undertaking different sports, each of which
is interspersed with long periods of inactivity. This hypothesis
thus holds that individuals might be responsible to a large
extent for the state of health of their cartilage, and implies
that regular exercise might better maintain cartilage in good
health. It also implicitly advises against sudden increases
in the level of activity, but recommends instead a gradual increase
when changing from a sedentary lifestyle to an athletic one.
The need for epidemiological studies into the association between
OA and activity is underscored.
|
Acknowledgments
|
|---|
The author would like to thank the colleagues and friends who
have read and commented on this document. The studies reported
were supported by the Arthritis Research Campaign.
The author has declared no conflicts of interest.
|
References
|
|---|
- Spector TD, Hart DJ, Doyle DV. Incidence and progression of osteoarthritis in women with unilateral knee disease in the general population: the effect of obesity. Ann Rheum Dis 1994;53:565–8.[Abstract/Free Full Text]
- Radin EL, Burr DB, Caterson B, Fyhrie D, Brown TD, Boyd RD. Mechanical determinants of osteoarthrosis. Semin Arthritis Rheum 1991;21:12–21.[Web of Science][Medline]
- Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG. Osteoarthritis: new insights. Part 1: The disease and its risk factors. Ann Intern Med 2000;133:635–46.
- Freund E. Joint cartilage under infraphysiologic, ultraphysiologic and euphysiologic demands. Arch Surg 1939;39:596–623.[Abstract/Free Full Text]
- Trueta, J. Studies in the aetiopathology of osteoarthritis of the hip. Clin Orthop 1963;31:7–19.[Medline]
- Goodfellow JW, Hungerford DS, Zindel M. Patello-femoral joint mechanics and pathology. In: Functional anatomy of the patello-femoral joint. J Bone Joint Surg 1976;58B:287–90.[Free Full Text]
- Byers PD, Contepomi CA, Farkas TA. A post mortem study of the hip joint. Including the prevalence of the features of the right side. Ann Rheum Dis 1970;29:15–31.[Free Full Text]
- Weightman B, Freeman MAR, Swann AC. Fatigue of articular cartilage. Nature 1973;244:303–4.[Medline]
- Freeman MAR, Meachim G. Ageing and degeneration. In: Freeman MAR, ed. Adult articular cartilage. 2nd edn. Tunbridge Wells: Pitman Medical, 1979:526–7.
- Weightman B. Tensile fatigue of human articular cartilage. J Biomech 1976;9:193–200.[CrossRef][Web of Science][Medline]
- Weightman B, Chappell DJ, Jenkins EA. A second study of tensile fatigue properties of human articular cartilage. Ann Rheum Dis 1978;37:58–63.[Abstract/Free Full Text]
- Kempson GE. Relationship between the tensile properties of articular cartilage from the human knee and age. Ann Rheum Dis 1982;41:508–11.[Abstract/Free Full Text]
- Kempson GE. Age-related changes in the tensile properties of human articular cartilage: a comparative study between the femoral head of the hip joint and the talus of the ankle joint. Biochim Biophys Acta 1991;1075:223–30.[Medline]
- Seedhom BB, Takeda T, Tsubuku M, Wright V. Mechanical factors and patellofemoral osteoarthrosis. Ann Rheum Dis 1979;38:307–16.[Abstract/Free Full Text]
- Meachim G. Light microscopy of Indian ink preparations of fibrillated cartilage. Ann Rheum Dis 1972;31:457–64.[Free Full Text]
- Meachim G, Emery IH. Quantitative aspects of patello-femoral cartilage fibrillation in Liverpool necropsies. Ann Rheum Dis 1974;33:39–47.[Free Full Text]
- Swann AC, Seedhom BB. The stiffness of normal articular cartilage and the predominant acting stress levels. Br J Rheumatol 1993;32:16–25.[Abstract/Free Full Text]
- Yao JQ, Seedhom BB. Mechanical conditioning of articular cartilage to prevalent stress. Br J Rheumatol 1993;33:16–25.
- Shepherd DET, Seedhom BB. The ‘instantaneous’ compressive modulus of human articular cartilage in joints of the lower limb. Rheumatology 1999;38:124–32.[Free Full Text]
- Treppo S, Koepp H, Quan EC, Cole AA, Kuettner KE, Grodzinsky AJ. Comparison of biomechanical and biochemical properties of cartilage from human knee and ankle pairs. J Orthop Res 2000;18:739–48.[CrossRef][Web of Science][Medline]
- Huch K, Kuettner KE, Dieppe P. Osteoarthritis in ankle and knee joints. Semin Arthritis Rheum 1997;26:667–74.[CrossRef][Medline]
- Hulth A. Does osteoarthrosis depend on growth of the mineralised layer of cartilage? Clin Orthop 1993;287:19–24.
- Dieppe PA, Kirwan J. The localization of osteoarthritis. Br J Rheumatol 1994;33:201–4.[Free Full Text]
- Cushnaghan J, Dieppe P. Study of 500 patients with limb joint osteoarthritis. I. Analysis by age, sex, and distribution of symptomatic joint sites, Ann Rheum Dis 1991;50:8–13.[Abstract/Free Full Text]
- Koepp H, Eger W, Muehleman C et al. Prevalence of articular cartilage degeneration in the ankle and knee joints of human organ donors. J Orthop Sci 1999;4:407–12.[CrossRef][Medline]
- Yao JQ, Seedhom BB. A new technique for measuring contact areas in human joints – ‘the 3-S technique’. Engineering in medicine, Part H. Proc Inst Mech Engineers 1991;205:69–72.
- Roos H, Laurén M, Adalberth T, Roos EM, Jonsson K, Lohmander LS. Knee osteoarthritis after meniscectomy: prevalence of radiographic changes after twenty-one years, compared with matched controls. Arthritis Rheum 1998;41:687–93.[CrossRef][Web of Science][Medline]
- Jackson JP. Degenerative changes in the knee after meniscectomy. Br Med J 1968;2:25.
- Shrive NG, O’Connor JJ, Goodfellow JW. Load-bearing in the knee joint. Clin Orthop 1978;131:279–87.
- Seedhom BB, Hargreaves DJ. Transmission of the load in the knee joint with special reference to the role of the menisci. Part II: Experimental results, discussion and conclusions. Eng Med 1979;8:220–8.[CrossRef]
- Kawakubo M, Seedhom BB. Knee ligamentous deficiency and patellar femoral contact stresses. J Bone Joint Surg 1996;78B (Suppl. I):35.
- Dahlkvist NM, Mayo P, Seedhom BB. Forces during squatting and rising from a deep squat. Eng Med 1982;1:69–76.
Submitted 16 August 2005;
revised version accepted 11 October 2005.
CiteULike 
Connotea 
Del.icio.us What's this?
Top
Abstract
Introduction