Epidemiology of osteoarthritis [619266]

21Chapter 2
Epidemiology of osteoarthritis
Definition of osteoarthritis
“ A group of overlapping disorders with different aetiologies but similar biologic,
morphologic and clinical outcomes. The disease processes affect articular cartilage,
subchondral bone, synovium, capsule and ligaments. Ultimately, cartilage degenerates
with fibrillation, fissures, ulceration and full thickness loss of joint surface. ”
Nigel Arden
This definition is itself developed from one coined by the Diagnostic and Therapeutic Criteria
Committee of the American Rheumatism Association for the development of criteria for clas –
sifying and reporting osteoarthritis in 1986 [1]. It also made the distinction between subclinical,
non-symptomatic defects in articular cartilage, which is poorly innervated, and the clinical
syndrome, which includes pain, that may develop from such defects [1].
“ Knee osteoarthritis is characterised clinically by usage-related pain and/or functional
limitation. It is a common complex joint disorder showing focal cartilage loss, new bone
formation and involvement of all joint tissues. Structural tissue changes are mirrored in
classical radiographic features. ”
The European League Against Rheumatism
“ A heterogeneous group of conditions that lead to joint symptoms and signs which are
associated with defective integrity of articular cartilage, in addition to related changes in
the underlying bone at the joint margins. ”
American College of Rheumatology
A specific definition of knee osteoarthritis was developed in 2010 for the European League Against
Rheumatism (EULAR) evidence-based recommendations for the diagnosis of knee osteoarthritis
[2]. The EULAR recommendations, which emphasise that knee osteoarthritis may associate with
osteoarthritis at other joints due to shared genetic and constitutional risk symptoms, also high –
light that the definition of knee osteoarthritis may change based on the different levels of care
needed and the clinical requirements [2].Cyrus Cooper, M. Kassim Javaid and Nigel Arden
This publication has been made possible through an educational grant from SERVIER.
N. Arden et al., Atlas of Osteoarthritis , DOI 10.1007/978-1-910315-16-3_2,
©Springer Healthcare 2014

22Classification of osteoarthritis
In 1957, Kellgren and Lawrence developed a classification system that sets out a series of radio –
logical features that are considered evidence of osteoarthritis, and divides the disease into five
grades (Figure 2.1) [3]:
• 0 – None
• 1 – Doubtful
• 2 – Minimal
• 3 – Moderate
• 4 – Severe
Grade 0 indicates a definite absence of osteoarthritis changes on a single anteroposterior X-ray,
while grade 2 represents definite osteoarthritis, albeit of minimal severity [3]. Although the system
is widely used, it has limitations, particularly when assessing individual radiographic features.
Radiographic classification of osteoarthritis
Figure 2.1 Radiographic
classification of
osteoarthritis.
A, Grade 1: doubtful joint
space narrowing (JSN)
and possible osteophytic
lipping.
B, Grade 2: definite
osteophytes and
possible JSN.
C, Grade 3: moderate
multiple osteophytes,
definite JSN, some
sclerosis, possible bone
end deformity.
D, Grade 4: large
osteophytes, marked
JSN, severe sclerosis
definite deformity of
bone ends. Image from
Kellgren & Lawrence [3].
© 1957, reproduced
with permission from
BMJ Publishing Group Ltd.A
B
C
D
Atlas of osteoarthritis

23Epidemiology of osteoarthritis
The radiological features of knee osteoarthritis were refined by the Osteoarthritis Research
Society International in 2007 [4], and divided into: the presence of marginal osteophytes in
the medial femoral condyle, medial tibial plateau, lateral femoral condyle and lateral tibial
plateau (Figure 2.2) [5] and joint space narrowing (JSN) of the medial compartment and lateral
compartment. Each of these are graded for degree of change:
• 0 – Normal
• 1 – Mild change
• 2 – Moderate change
• 3 – Severe change
Figure 2.2 Femoral
osteophytes. This coronal
magnetic resonance image
of an osteoarthritis knee is
a T1-weighted spin-echo
image that shows femoral
osteophytes on the medial
and lateral aspects of the
joint. The bright signal
within the osteophytes
is produced by marrow
fat. Reproduced with
permission from Myers [5].Femoral osteophytes
Recently, a Delphi exercise was undertaken to develop definitions of osteoarthritis on mag –
netic resonance imaging (MRI), which suggested that, while MRI changes of osteoarthritis may
occur in the absence of radiographic findings, MRI changes in isolation and single MRI changes,
are not diagnostic of osteoarthritis [6]. Nevertheless, a definition of tibiofemoral osteoarthritis
on MRI was developed (Figure 2.3, see page 22) [7], which was either the presence of two features
from group A, or one group A feature plus at least two group B features, where:
• Group A, after exclusion of joint trauma within the last 6 months and exclusion of
inflammatory arthritis:
−Definite osteophyte formation
−Full thickness cartilage loss
• Group B:
−Subchondral bone marrow lesion or cyst not associated with meniscal or
ligamentous attachments
−Meniscal subluxation, maceration or degenerative (horizontal) tear
−Partial thickness cartilage loss (where full thickness loss is not present)
−Bone attrition

24A composite model was created using the above features to assess the ability of MRI to detect
radiographic osteoarthritis compared with Kellgren and Lawrence (KL) grade 2, which yielded
a C statistic of 0.59, which was described by the authors as “disappointing” [6]. Nevertheless,
MRI retains the potential to diagnose osteoarthritis earlier than the current reference standard
of radiography [6].
Prevalence and incidence of osteoarthritis
The prevalence of osteoarthritis has been assessed in a number of studies spanning several
decades. van Saase et al examined the prevalence of mild and severe radiological osteoarthritis
in a single Dutch village, finding that increased radiological osteoarthritis is strongly linked to
age, regardless of whether small or large weight-bearing joints are considered, and holds for
both men and women (Figure 2.4) [8].
The highest prevalence for osteoarthritis is seen in the cervical spine, the lumbar spine and
the distal interphalangeal joints (DIP) [8]. Severe radiological osteoarthritis is uncommon under
age 45 years, and the prevalence does not exceed 20% in the elderly aside from in the cervical
and lumbar spine and DIP and, in women, the joints of the hands and the knees [8]. Significant sex
differences are seen in the knees, in the hips among those aged at least 65 years and in the DIP
of the hands [8]. Comparison with other populations shows that, although there are substantial
differences between populations for individual joints, the slope of the majority of lines is similar
for individual and groups of joints, with no one population having a low or high prevalence of
osteoarthritis for all joints [8].Figure 2.3 Magnetic
resonance imaging of
the knee: remodelling and
sclerosis. This magnetic
resonance image reveals
considerable subchondral
bone remodelling and
sclerosis. Posteriorly,
the cartilage of the lateral
compartment is thickened
with thinning and irregular
cartilage in the medial
compartment. Reproduced
with permission from
Altman [7].Magnetic resonance imaging of the knee: remodelling and sclerosis
Atlas of osteoarthritis

25The incidence of osteoarthritis increases with age, and women have higher incidences than
men, especially after age 50 (Figure 2.5, see page 24) [9]. The incidence of knee osteoarthritis
is twice that of hand or hip osteoarthritis, and the female:male sex ratio for hand, hip and knee
osteoarthritis is approximately 2:1. The trend of increasing osteoarthritis incidence continues
until age 80 after which there is a levelling off or decline in the rates for all joints, which may be
linked to sedentary activity in older age groups [9].
The lifetime risk of undergoing total hip replacement (THR) or total knee replacement (TKR) is
lower than that of developing symptomatic knee or hip osteoarthritis [10]. The mortality-adjusted
lifetime risk of undergoing THR at age 50 years is estimated, using 2005 data, at 11.6% for women
and 7.1% for men, while the risks of undergoing TKR are 10.8% and 8.1%, respectively [10].
The risk decreases with increasing age for THR and TKR in both men and women, such that, at 80
years of age, the lifetime risk of THR is 3.8% for women and 2.7% for men, while that for TKR is
3.3% and 2.7%, respectively [10].Figure 2.4 Prevalence of
osteoarthritis. A random
sample of a Dutch village
demonstrated the high
prevalence of radiological
osteoarthritis, which
increases progressively
with age. Mild radiological
osteoarthritis is more
prevalent in women ( B)
than in men ( A), while
severe radiological
osteoarthritis is
substantially more
prevalent in women.
DIP , distal interphalangeal
joints. Data from
van Saase et al [8].
© 1989, reproduced
with permission from
BMJ Publishing Group Ltd.Prevalence of osteoarthritis
DIP
Knee
Hip80
60
40
20
0
20 30 40 50 60 70 80
Age (years)Prevalence of osteoarthritis (%)A Men
80
60
40
20
0
20 30 40 50 60 70 80
Age (years)Prevalence of osteoarthritis (%)B Women DIP
Knee
HipEpidemiology of osteoarthritis

26Incidence of osteoarthritis of the hand, hip and knee by age and sex
Figure 2.5 Incidence
of osteoarthritis of the
hand, hip and knee by
age and sex. The data
represents incidence
in members of the
Fallon Community
Health Plan, 1991–1992.
A, The equivalent
figures for men were
5 per 100,000 person-
years and 619 per
100,000 person-years.
B, Among women, the
incidence rates for knee
osteoarthritis ranged from
0 per 100,000 person-
years among those aged
20–29 years to 1082 per
100,000 person-years for
those aged 70–79 years.
The overall age- and sex-
standardised incidence
rate for knee osteoarthritis
was 240/100,000 person-
years (95% CI 218–262).
Adapted from Oliveria
et al [9].
Interestingly, the rates of primary TKR have increased substantially over the last two
decades, much more so than for THR (Figure 2.6) [11]. This may reflect the more recent matura –
tion of TKR as an efficacious treatment for osteoarthritis, or be because the number TKRs per –
formed each year is below that which would be appropriate for the burden of osteoarthritis of
the knee [11].Hand
Knee
HipIncidence of osteoarthritis (%)900
800
700
600
500
400
300
200
100
0B Women
20 30 40 50 60 70 80
Age (years)A Men
1200
1100
1000
900
800
700
600
500
400
300
200
100
0
20 30 40 50 60 70 80
Age (years)Incidence of osteoarthritis (%)Atlas of osteoarthritis

27Aetiology and risk factors
In order to understand the influence that risks factors for osteoarthritis have on the pathogenesis,
a conceptual framework for the disease has been developed in recent years that consists of the
following tenets (Figure 2.7) [12–18]:Trends in primary total knee replacement rates
Figure 2.6 Trends in
primary total knee
replacement rates.
During the study
period (1991–2006),
the estimated
age-standardised rates
of primary total knee
replacement (TKR)
increased from
42.5 (95% CI 37.0–48.0) to
138.7 (95% CI 132.3–145.0)
in women and from
28.7 (95% CI 23.9–33.6) to
99.4 (95% CI 93.9–104.8)
in men. Interestingly, there
was a marked plateau
in TKR rates from the
mid-1990s, followed by
a sharp rise from 2000.
Data from Culliford et al
[11]. © 2012, reproduced
with permission from The
British Editorial Society of
Bone and Joint Surgery.Female
Male160
140
120
100
80
60
40
20
0
YearsRate (per 100,000 person-years)
1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Figure 2.7 Risk factors
for osteoarthritis. Several
systemic factors have been
identified as risk factors for
knee osteoarthritis, which
may act by increasing
the susceptibility of
joints to injury, via direct
damage to joint tissues,
or by impairing the repair
process in damaged joint
tissue. Local biomechanical
factors are, in contrast,
believed primarily to
determine the exposure of
individual joints to injury
and to excess loading that
leads to joint degeneration.
Adapted from [16–18]. Risk factors for osteoarthritis
Susceptibility to osteoarthritis or to its progressionSystemic factors:
1. Age
2. Gender
3. Ethnic
4. Hormonal status
5. Genetic factors
6. Bone density
7. Nutritional factors
(vitamin C and D are protective)
8. InflammationLocal joint factors:
1. Previous damage
2. Muscle weakness
3. Joint deformity/
incongruity
4. Ligamentous laxityExtrinsic factors acting
on joints:
1. Obesity
2. Specific injurious activities:
• Sport and physical
activities (excess)
• Occupational factors
(eg, farming)
• Cartilage, bone, muscles, ligaments and other joint tissues and structures function as
a biomechanical organ system that maintains proper movement and prevents excessive
joint loading;
• Systemic factors that increase overall susceptibility to joint degeneration, and local
biomechanical factors that impair the optimal functioning of a joint both play an important
role in determining the risk of developing osteoarthritis; andEpidemiology of osteoarthritis

28• Systemic factors interact with mechanical factors operating within the local joint
environment to determine which joints develop osteoarthritis and how rapidly the disease
progresses in an affected joint.
It is suggested that several of the pathological features of osteoarthritis, including proliferative
bone changes, may represent attempts to repair the injured joint [19]. For example, osteophytes
may arise from a reactive response of cartilage and bone to abnormal mechanical loading, thus
reducing instability to protect the damaged joint [12]. Systemic and local factors may act in a
joint-specific manner to determine whether such a response is normal or aberrant, and whether
it succeeds or fails in protecting the joint [12]. There are a number of factors associated with
osteoarthritis of the knee, hip and hand.
Age
The age-related increases in osteoarthritis prevalence and incidence are particularly pronounced
in the commonly affected joints, such as the knee, hip and hand. It is thought that the relation –
ship between age and the risk of osteoarthritis is mediated by age-related increases in a range
of systemic and biomechanical risk factors [12].
Sex
Female gender amplifies the age-related increase in osteoarthritis risk in the hands and knees,
as well as osteoarthritis in multiple joints, such that, after 50 years of age, the prevalence and
incidence is significantly greater in women than men [9,20]. While hip osteoarthritis appears to
progress more rapidly in women [21,22], there appears to be no gender impact on knee [23,24],
or hand osteoarthritis progression [12].
Ethnicity
The prevalence of osteoarthritis and patterns of affected joints vary among racial and ethnic
groups [25]. Osteoarthritis is, in general, more prevalent in Europe and the USA than other parts of
the world [26]. Osteoarthritis of the knee is more common in African-American women than white
women [27], but that is not the case for the hip [28]. Osteoarthritis of the hip is more common
in European whites than in Jamaican blacks [29], African blacks [30] or Chinese [31]. The Beijing
Osteoarthritis Study indicated that hip and hand osteoarthritis was less frequent among Chinese
than in whites in the Framingham Study, although the prevalence of radiographic and symptomatic
knee osteoarthritis was significantly higher in Chinese women than in white women [32,33].
Menopause
As the increase in the age-related rise in osteoarthritis occurs following menopause, it would
suggest that sex hormones, particularly oestrogen deficiency, play a role in the systemic pre –
disposition to osteoarthritis [12]. While many studies have looked at the possibility of lowering
osteoarthritis risk through oestrogen use, any associations may be misleading, as oestrogen
use is linked to a healthy lifestyle and osteoporosis, which lowers the risk of osteoarthritis [12].Atlas of osteoarthritis

29Genetic factors
Genetic vulnerability appears to account for approximately half the variability of susceptibility
to hand, hip and knee osteoarthritis in women [34–40] and men [38,39]. These studies suggest
that not only are multiple genes likely to be involved in osteoarthritis susceptibility but also
that environmental factors have an important role in progression [12]. The search for candidate
genes has focused on genes encoding type II collagen (the primary collagen in articular cartilage),
structural proteins of the extracellular cartilage matrix, the vitamin D and oestrogen receptor
genes, as well as encoding bone and cartilage growth factors [41].
Obesity
Obesity is one of the most well-established and strongest risk factors for knee osteoarthritis [13], and
precedes the development of knee osteoarthritis by many years [42–44]. In addition, obesity acceler –
ates the progression of knee osteoarthritis [45,46]. The primary mechanism for the impact of obesity
of knee osteoarthritis is likely to be excess weight on overloading of the joints during weight-bearing
activities, leading to breakdown of cartilage and damage to ligaments and other support structures
[12]. Metabolic factors, such as circulating adipocytokines, adiposity-linked glucose and lipid abnor –
malities and chronic inflammation, may also play a role in the pathogenesis of osteoarthritis [12].
Mechanical and occupational factors and trauma
Acute knee injuries, including meniscal and cruciate ligament tears in the knee, fractures and disloca –
tions [12], substantially increase the risk of any subsequent osteoarthritis, as well that of more severe
disease [45]. In addition, the risk of osteoarthritis is increased by weekly participation in sports for a
decade or longer after leaving school [44]. Specifically, repetitive and excessive joint loading due to
specific physical activities increases the risk of developing osteoarthritis in the stressed joints [12].
Congenital and developmental diseases
The risk of developing osteoarthritis is substantially increased as a result of congenital abnormali –
ties that result in abnormal load distributions within the joint [47]. As the mechanical alignment
of the knee, as determined by the hip/knee/ankle angle, is an important determinant of load
distribution of the knee during ambulation [48], varus and valgus malalignment are found with
a high frequency in knees with evidence of osteoarthritis involvement of the medial and lateral
components, respectively [49]. Osteoarthritic knees with varus malalignment have a three- to
fourfold increased risk of further joint space narrowing in the medial compartment, which is
similar to the increased risk of further lateral compartment joint space narrowing in osteoarthritis
knees with valgus malalignment [50]. Discoveries about the pathophysiology of the disease have
led to a potential division of the disease into distinct phenotypes (see Table 1.1) [51]. In addition
to improving our understanding of the disease, classifying the different clinical and structural
phenotypes of osteoarthritis allows for more direct targeting of treatments, depending on where
the predominate structural changes are, eg, cartilage, bone or synovial tissue. However, there is
currently no consensus on the subgrouping of osteoarthritis into these phenotypes [51].Epidemiology of osteoarthritis

30Disease course and determinants of osteoarthritis progression
There are a number of biomarkers under investigation for the assessment of osteoarthritis
progression, as the identification of rapid progressors would assist in the development and
targeting of therapies. Imaging technologies such as MRI appear promising in the assessment of
disease progression, and combining biochemical and MRI-based biomarkers may offer effective
diagnostic and prognostic tools for identifying osteoarthritis patients at high risk of progression
(Figure 2.8) [52]. While cartilage roughness is a good diagnostic marker, with an area under the
receiver operating characteristics curve (AUC) of 0.80, and cartilage homogeneity performs well
as a prognostic marker, with an AUC of 0.71, an aggregate marker of cartilage matrix breakdown
and cartilage volume, thickness, area, congruity, roughness and homogeneity performs well both
diagnostically and prognostically, at respective AUCs of 0.84 and 0.77 [52].
Figure 2.9 Clinical and
epidemiological studies
on the progression of knee
osteoarthritis. Circles
represent the timings of
the visits for the Chingford
study. Figure courtesy of
Dr K Leyland. Data from
[45,46,53–58].Clinical and epidemiological studies on the progression of knee osteoarthritis
Pain
StructureYears5 10 15
Cooper 2000 [45] Spector 1992 [54]
Massardo 1989 [53] Thorstensson 2008 [55]
Hernborg & Nilson 1977 [56]Schouten 1992 [46]
Other
Lachance 2002 [57] Felson 1995 [58] Chingford studyOsteoarthritis stages, biomarkers and interventions
Figure 2.8 Osteoarthritis
stages, biomarkers and
interventions. Figure
courtesy of Dr C Cooper.
Osteoarthritis progressionCartilage quantityCongruity
Homogeneity
Smoothness
Focal thickness
Volume/thicknessPrevention
Cartilage regeneration
Stabilisation
DisabilityPainAtlas of osteoarthritis

31There have been a number of studies that have examined the progression of osteoarthri-
tis over follow-up periods of up to 15 years, including the recently published Chingford study
(Figure 2.9) [45,46,53–58].
The evolution of knee osteoarthritis is slow, it typically takes several years and can remain
stable for several years [21]. Radiographic deterioration is seen in a third to two-thirds of osteo-
arthritis patients and radiographic improvement is unusual (Table 2.1) [45,46,53,54,59–65].
Table 2.1 Natural history
of knee osteoarthritis.
C, Clinical; R, Radiographic.
Table adapted with
permission from Dennison
& Cooper [65]. Data from
[45,46,53,54,59–64].Natural history of knee osteoarthritis
Study N Measure Years Deterioration (%)
Hernborg & Nilson (1977) [56] 94 C
R15
1555
56
Danielsson (1970) [59] 106 R 15 33
Massardo (1989) [53] 31 R 8 42
Dougados (1992) [60] 353 C
R1
128
29
Schouten (1992) [46] 142 R 12 34
Spector (1992) [54] 63 R 11 33
Spector (1994) [61] 58 R 2 22
Ledingham (1995) [62] 350 R 2 72
McAlindon (1999) [63] 470 R 4 11
Cooper et al (2000) [45] 354 R 5 22
Felson (2004) [64] 323 R 2.5 28
While there are several factors signifi cantly associated with the incidence of osteoar-
thritis, only obesity is signifi cantly individually linked to the progression of grade 1+ disease
(Figure 2.10) [45]. In addition, the coexistence of Heberden’s nodes with knee osteoarthritis
increases the risk of knee deterioration by almost sixfold [21].Odds ratio of incidence and progression of knee osteoarthritis
Figure 2.10 Odds ratio of
incidence and progression
of knee osteoarthritis.
The odds ratio (OR) was
calculated over 5 years
among patients with
Kellgren and Lawrence
grade 1+ disease. OR are
adjusted for age and sex
in all cases. In addition,
OR for BMI, knee pain
and Heberden’s nodes
are mutually adjusted.
OR for knee injury and
sports participation are
adjusted for age, sex, BMI,
knee pain and Heberden’s
nodes. Obesity was a strong
predictor of incidence knee
osteoarthritis ( P<0.001)
and a significant predictor
of progression ( P<0.05).
BMI, Body mass index;
CI, confidence interval.
*Significant increase in risk.
Data from Cooper et al [45]. Incidence
Progression100
10
1
0.1
BMI
(kg/m2)Knee pain
(baseline)Heberden’s
nodesPrevious
knee injuryRegular
sportOR (95% CI)* **
**
*Epidemiology of osteoarthritis

32The Chingford study looked at the progression of individual KL grades over 15 years
(Table 2.2) [66], which revealed that approximately half of knees had a KL grade of 0 throughout,
while two-fifths worsened by at least one grade. Knees with baseline KL grade 1 had a higher
percentage of progression, at almost three-quarters, than knees with any other KL grade at base –
line. Less than 2% of knees were scored as having regressed to a lower KL grade by year 15 [43].
Table 2.2 Progression
of individual Kellgren
and Lawrence grades
over 15 years. Data from
Leyland et al [66].Progression of individual Kellgren and Lawrence grades over 15 years
Baseline Kellgren
and
Lawrence grade NYear 15 Kellgren and Lawrence grade
0 1 2 3 4 5
0 905 60.1% (548) 9.9% (90) 15.7% (142) 12.5% (113) 0.1% (1) 1.2% (11)
1 57 19.3% (11) 5.3% (3) 40.4% (23) 29.8% (17) 0.0% (0) 5.3% (3)
2 60 0 (0.0%) 1.7% (1) 50.0% (30) 41.7% (25) 0.0% (0) 6.7% (4)
3 26 0.0% (0) 3.8% (1) 15.4% (4) 65.4% (17) 11.5% (3) 3.8% (1)
The prevalence of long-term knee pain is dependent on whether there was any pain at
baseline (Figure 2.11) [67]. The presence of knee osteoarthritis increases the risk of persistent
pain by 3.70-fold, while reported knee injury increases the risk of persistent pain 4.13-fold and
intermittent pain 4.25-fold [44]. Interestingly, there is a discrepancy between the presence
of radiographic osteoarthritis and corresponding pain, which may be due to KL grade being a
predictor only of persistent, and not intermittent pain.
Figure 2.11 Prevalence of
self-reported knee pain.
Bars show the means with
95% confidence intervals.
Individuals without knee
pain at baseline (year 3)
had an increase in pain
prevalence with duration
of follow-up, such that, at
year 15, the prevalence
was 35.2% for those
reporting any days of pain.
Data from Soni et al [67]. Prevalence of self-reported knee pain
100
90
80
70
60
50
40
30
20
10
0
Year 3 Year 5 Year 10 Year 15
VisitPrevalence of knee pain (%)No pain at year 3
Any pain at year 3Atlas of osteoarthritis

33Figure 2.12 Comorbidities suffered by osteoarthritic patients. COPD, chronic obstructive pulmonary disorder;
ECG, electrocardiography. Data from Datamonitor [69].Comorbidities suffered by osteoarthritic patients
40
35
30
25
20
15
10
5
0
Comorbidity% of comorbidities
Obesity
Hypertension
High cholesterolDyspepsia
Diabetes mellitus
GastroesophageaI reflux diseaseDepression
Previous traumaAbnormal ECG
Neurotic disordersRheumatoid arthritis
Ischaemic heart diseasePeptic ulcer diseaseFibromyalgia COPD/asthma
Irritable bowel syndromeAlcoholismGout
Congestive heart failureDementia
Gastroduodenal bleedingAnother important consideration in the assessment of osteoarthritis is the presence of
comorbidities. It is estimated that older osteoarthritis patients have an average of 8.7 chronic
medical diseases [68]. The three most common comorbidities are obesity, hypertension and high
cholesterol levels (Figure 2.12) [69].
References
1 Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of
osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and therapeutic criteria
committee of the American Rheumatism Association. Arthritis Rheum . 1986;29:1039-1049.
2 Zhang W, Doherty M, Peat G, et al. EULAR evidence-based recommendations for the diagnosis of
knee osteoarthritis. Ann Rheum Dis . 2010;69:483-489.
3 Kellgren J, Lawrence J. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957;16:494-502.
4 Altman R, Gold G. Atlas of individual radiographic features in osteoarthritis, revised. Osteo Cart.
2007;15 Suppl A:A1-56.
5 Myers S. Osteoarthritis and crystal-associated synovitis. In: Hunder G, ed. Atlas of Rheumatology.
4th ed. Philadelphia: Current Medicine Group; 2005:54-64.
6 Hunter D, Arden N, Conaghan P, et al. Definition of osteoarthritis on MRI: results of a Delphi exercise.
Osteo Cart. 2011;19:963-969.
7 Altman R. Osteoarthritis in the elderly population. In: Nakasato Y, Yung R, eds.
Geriatric Rheumatology. A Comprehensive Approach. New York: Springer; 2011:187-196.Epidemiology of osteoarthritis

34Atlas of osteoarthritis
8 van Saase JL, Van Romunde LK, Cats A, Vandenbroucke J, Valkenburg H. Epidemiology of
osteoarthritis: Zoetermeer survey. Comparison of radiological osteoarthritis in a Dutch population
with that in 10 other populations. Ann Rheum Dis. 1989;48:271-280.
9 Oliveria S, Felson D, Reed J, Cirillo P, Walker A. Incidence of symptomatic hand, hip, and knee
osteoarthritis among patients in a health maintenance organization. Arthritis Rheum.
1995;38:1134-1141.
10 Culliford D, Maskell J, Kiran A, et al. The lifetime risk of total hip and knee arthroplasty: results from
the UK General Practice Research Database. Osteo Cart. 2012;20:519-524.
11 Culliford D, Maskell J, Beard D, Murray D, Price A, Arden N. Temporal trends in hip and knee
replacement in the United Kingdom: 1991 to 2006. J Bone Joint Surg Br. 2010;92:130-135.
12 Arden N, Nevitt M. Osteoarthritis: Epidemiology. Best Pract Res Clin Rheumatol. 2006;20:3-25.
13 Felson D, Lawrence R, Dieppe P, et al. Osteoarthritis: new insights. Part 1: The disease and its risk factors.
Ann Intern Med. 2000;133:635-646.
14 Dieppe P. The classification and diagnosis of osteoarthritis. In: Kuettner K, Vm G, eds. Osteoarthritic
Disorders . Rosemont, IL: American Academy of Orthopedic Surgeons; 1995:5-12.
15 Sharma H, Hanna A, Titterington L, Stephens R. Effect of MAK -4 and MAK -5 on endothelial cell and
soyabean lipoxygenase-induced LDL oxidation. Adv Exp Med Biol. 1994;366:441-443.
16 Garstand S. Osteoarthritis: epidemiology, risk factors and pathophysiology. Am J Phys Med Rehabil .
2006;85: S2-S11.
17 Zhang Y, Jordan J. Epidemiology of osteoarthritis. Clin Geriatr Med . 2010;26:355-369.
18 Woolf A, Pfleger B. Burden of major musculoskeletal conditions. WHO Bulletin . 2003;81:646-656.
19 Dieppe P. Subchondral bone should be the main target for the treatment of pain and disease
progression in osteoarthritis. Osteo Cart. 1999;7:325-326.
20 Kellgren J, Moore R. Generalized osteoarthritis and Heberden’s nodes. Br Med J. 1952;1:181-187.
21 Dougados M, Gueguen A, Nguyen M, et al. Radiological progression of hip osteoarthritis: definition,
risk factors and correlations with clinical status. Ann Rheum Dis. 1996;55:356-362.
22 Loeser R, Shakoor N. Aging or osteoarthritis: which is the problem? Rheum Dis Clin North Am.
2003;29:653-673.
23 Felson D, Naimark A, Anderson J, Kazis L, Castelli W, Meenan R. The prevalence of knee osteoarthritis
in the elderly. The Framingham osteoarthritis study. Arthritis Rheum. 1987;30:914-918.
24 Ledingham J, Dawson S, Preston B, Milligan G, Doherty M. Radiographic progression of hospital
referred osteoarthritis of the hip. Ann Rheum Dis. 1993;52(4):263-267.
25 Zhang Y, Jordan J. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010;26:355-369.
26 Woolf A, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ.
2003;81:646-656.
27 Anderson J, Felson D. Factors associated with osteoarthritis of the knee in the first national Health
and Nutrition Examination Survey (HANES I). Evidence for an association with overweight, race, and
physical demands of work. Am J Epidemiol. 1988;128:179-189.
28 Tepper S, Hochberg M. Factors associated with hip osteoarthritis: data from the first National Health
and Nutrition Examination Survey (NHANES-I). Am J Epidemiol. 1993;137:1081-1088.
29 Bremner J, Lawrence J, Miall W. Degenerative joint disease in a Jamaican rural population.
Ann Rheum Dis. 1968;27:326-332.
30 Solomon L, Beighton P, Lawrence J. Rheumatic disorders in the South African negro. Part II.
Osteo-arthrosis. S Afr Med J. 1975;49:1737-1740.
31 Hoaglund F, Yau A, Wong W. Osteoarthritis of the hip and other joints in southern Chinese in
Hong Kong. J Bone Joint Surg Am. 1973;55:545-557.
32 Nevitt M, Xu L, Zhang Y, et al. Very low prevalence of hip osteoarthritis among Chinese elderly
in Beijing, China, compared with whites in the United States: the Beijing osteoarthritis study.
Arthritis Rheum. 2002;46:1773-1779.
33 Zhang Y, Xu L, Nevitt M, et al. Lower prevalence of hand osteoarthritis among Chinese subjects
in Beijing compared with white subjects in the United States: the Beijing osteoarthritis study.
Arthritis Rheum. 2003;48:1034-1040.
34 Macgregor A, Antoniades L, Matson M, Andrew T, Spector T. The genetic contribution to
radiographic hip osteoarthritis in women: results of a classic twin study. Arthritis Rheum.
2000;43:2410-2416.

3536 Kaprio J, Kujala U, Peltonen L, Koskenvuo M. Genetic liability to osteoarthritis may be greater in
women than men. BMJ. 1996;313:232.
37 Felson D, Couropmitree N, Chaisson C, et al. Evidence for a Mendelian gene in a segregation
analysis of generalized radiographic osteoarthritis: the Framingham study. Arthritis Rheum.
1998;41:1064-1071.
38 Lanyon P, Muir K, Doherty S, Doherty M. Assessment of a genetic contribution to osteoarthritis of
the hip: sibling study. BMJ. 2000;321:1179-1183.
39 Ingvarsson T, Stefansson S, Hallgrimsdottir I, et al. The inheritance of hip osteoarthritis in Iceland.
Arthritis Rheum. 2000;43:2785-2792.
40 Jonsson H, Manolescu I, Stefansson S, et al. The inheritance of hand osteoarthritis in Iceland.
Arthritis Rheum. 2003;48:391-395.
41 Loughlin J. Genetic epidemiology of primary osteoarthritis. Curr Opin Rheumatol. 2001;13:111-116.
42 Felson D, Zhang Y, Hannan M, et al. Risk factors for incident radiographic knee osteoarthritis in
the elderly: the Framingham study. Arthritis Rheum. 1997;40:728-733.
43 Spector T, Hart D, Doyle D. Incidence and progression of osteoarthritis in women with unilateral knee
disease in the general population: the effect of obesity. Ann Rheum Dis. 1994;53:565-568.
44 Gelber A, Hochberg M, Mead L, Wang N, Wigley F, Klag M. Body mass index in young men and the risk
of subsequent knee and hip osteoarthritis. Am J Med. 1999;107:542-548.
45 Cooper C, Snow S, McAlindon T, et al. Risk factors for the incidence and progression of radiographic
knee osteoarthritis. Arthritis Rheum. 2000;43:995-1000.
46 Schouten J, Van Den Ouweland FA, Valkenburg H. A 12 year follow up study in the general population
on prognostic factors of cartilage loss in osteoarthritis of the knee. Ann Rheum Dis. 1992;51:932-937.
47 Harris W. Etiology of osteoarthritis of the hip. Clin Orthop Relat Res. 1986;213:20-33.
48 Andriacchi T. Dynamics of knee malalignment. Orthop Clin North Am . 1994;25:395-403.
49 Felson D, Nevitt M, Zhang Y, et al. High prevalence of lateral knee osteoarthritis in Beijing Chinese
compared with Framingham caucasian subjects. Arthritis Rheum. 2002;46:1217-1222.
50 Sharma L, Song J, Felson D, Cahue S, Shamiyeh E, Dunlop D. The role of knee alignment in disease
progression and functional decline in knee osteoarthritis. JAMA. 2001;286:188-195.
51 Bijlsma JWJ, Berenbaum F, Lafeber FPJG. Osteoarthritis: an update with relevance for clinical
practice. Lancet . 2011;377:2115-2126.
52 Dam E, Loog M, Christiansen C, et al. Identification of progressors in osteoarthritis by combining
biochemical and MRI-based markers. Arthritis Res Ther . 2009;11:R115.
53 Massardo L, Watt I, Cushnaghan J, Dieppe P. Osteoarthritis of the knee joint: an eight year prospective
study. Ann Rheum Dis . 1989;48:893-897.
54 Spector TD, Dacre JE, Harris PA, Huskisson EC. Radiological progression of osteoarthritis: an 11 year
follow up study of the knee. Ann Rheum Dis. 1992;51:1107-1110.
55 Thorstensson CA, Andersson ML, Jönsson H, Saxne T, Petersson IF. Natural course of knee osteoarthritis
in middle-aged subjects with knee pain: 12-year follow-up using clinical and radiographic criteria.
Ann Rheum Dis. 2009;68:1890-1893.
56 Hernborg JS, Nilsson BE. The natural course of untreated osteoarthritis of the knee. Clin Orthop
Relat Res. 1977;123:130-137.
57 Lachance L, Sowers MF, Jamadar D, Hochberg M. The natural history of emergent osteoarthritis of
the knee in women. Osteoarthr Cartil. 2002;10:849-854.
58 Felson DT, Zhang Y, Hannan MT, et al. The incidence and natural history of knee osteoarthritis in
the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum . 1995;38:1500-1505.
59 Danielsson L, Hernborg J. Morbidity and mortality of osteoarthritis of the knee (gonarthrosis) in
Malmö, Sweden. Clin Orthop Relat Res . 1970;69:224-226.
60 Dougados M, Gueguen A, Nguyen M, et al. Longitudinal radiologic evaluation of osteoarthritis of
the knee. J Rheumatol . 1992;19:378-384.
61 Spector TD, Hochberg MC. Methodological problems in the epidemiological study of osteoarthritis.
Ann Rheum Dis. 1994;53:143-146.
62 Ledingham J, Regan M, Jones A, Doherty M. Factors affecting radiographic progression of knee
osteoarthritis. Ann Rheum Dis. 1995;54:53-58.Epidemiology of osteoarthritis
35 Spector T, Cicuttini F, Baker J, Loughlin J, Hart D. Genetic influences on osteoarthritis in women: a twin
study. BMJ. 1996;312:940-943.

3665 Dennison E, Cooper C. The natural history and prognosis of osteoarthritis. In: Brandt K, Doherty M,
Lohmander M, eds. Textbook of Osteoarthritis . 2nd ed. Oxford: Oxford University Press; 2003:227-233.
66 Leyland KM, Hart DJ, Javaid MK, et al. The natural history of radiographic knee osteoarthritis:
a fourteen-year population-based cohort study. Arthritis Rheum. 2012;64:2243-2251.
67 Soni A, Kiran A, Hart D, et al. Prevalence of reported knee pain over twelve years in a community-based
cohort. Arthritis Rheum. 2012;64:1145-1152.
68 Bayliss E, Ellis J, Steiner J. Barriers to self-management and quality-of-life outcomes in seniors with
multimorbidities. Ann Fam Med. 2007;5:395-402.
69 Datamonitor. Stakeholder Insight: Osteoarthritis. Drug development lags behind rising osteoarthritis
population. Datamonitor Europe: London, UK; December 2009.Atlas of osteoarthritis
64 Felson DT, Neogi T. Osteoarthritis: is it a disease of cartilage or of bone? Arthritis Rheum . 2004;50:341-344.63 McAlindon TE, Wilson PW, Aliabadi P, Weissman B, Felson DT. Level of physical activity and the risk of
radiographic and symptomatic knee osteoarthritis in the elderly: the Framingham study. Am J Med .
1999;106:151-157.

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