Osteoarthritis and Cartilage 30 (2022) 184e195

Epidemiology of osteoarthritis
K.D. Allen y z x *, L.M. Thoma y ¦, Y.M. Golightly y ¦ ¶ #
y Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
z Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
x Center for Health Services Research in Primary Care, Department of Veterans Affairs Medical Center, Durham, NC, USA
¦ Division of Physical Therapy, Department of Allied Health Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
¶ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
# Injury Prevention Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

a r t i c l e i n f o s u m m a r y

Article history: Objective: To summarize the current state of the evidence regarding osteoarthritis (OA) prevalence,
Received 30 July 2020 incidence and risk factors at the person-level and joint-level.
Accepted 19 April 2021 Design: This was a narrative review that took a comprehensive approach regarding inclusion of potential
risk factors. The review complements prior reviews of OA epidemiology, with a focus on new research
Keywords: and emerging topics since 2017, as well as seminal studies.
Osteoarthritis
Results: Studies continue to illustrate the high prevalence of OA worldwide, with a greater burden among
Epidemiology
older individuals, women, some racial and ethnic groups, and individuals with lower socioeconomic
Risk factors
status. Modifiable risk factors for OA with the strongest evidence are obesity and joint injury. Topics of
high interest or emerging evidence for a potential association with OA risk or progression include specific
vitamins and diets, high blood pressure, genetic factors, metformin use, bone mineral density, abnormal
joint shape and malalignment, and lower muscle strength/quality. Studies also continue to highlight the
heterogenous nature of OA, with strong interest in understanding and defining OA phenotypes.
Conclusions: OA is an increasingly prevalent condition with worldwide impacts on many health out-
comes. The strong evidence for obesity and joint injury as OA risk factors calls for heightened efforts to
mitigate these risks at clinical and public health levels. There is also a need for continued research
regarding how potential person- and joint-level risk factors may interact to influence the development
and progression of OA.
Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.

Introduction from earlier work, particularly seminal studies and topics not
represented newer studies. Similar to some other reviews, potential
Osteoarthritis (OA) is a disease involving multiple anatomic and risk factors are grouped according to person-level and joint-level
physiological alterations of joint tissues, including cartilage characteristics. We note that this review does not include a review
degradation, bone remodeling and osteophyte formation; this leads of spine OA or genetic factors associated with OA, as these will be
to clinical manifestations including pain, stiffness, swelling and covered in separate manuscripts in this series4.
limitations in joint function1. OA is one of the most common
chronic health conditions, impacting not only pain and physical
OA prevalence and incidence
function but also many other outcomes including mental health,
sleep, work participation, and even mortality1. Because there have
Table I provides estimates of radiographic and symptomatic OA
been prior reviews of OA epidemiology2,3, this narrative review
prevalence and incidence from recent cohort studies (2017 to
emphasizes new research since 2017. However, we include results
present), along with details on sample weights when appropriate;
the text below also summarizes data from key earlier studies, with
come cohort studies from China being described in the De-
* Address correspondence and reprint requests to: K.D. Allen, Thurston Arthritis
Research Center, The University of North Carolina at Chapel Hill, 3300 Thurston
mographic Characteristics section. Estimates have varied across
Bldg., CB# 7280, Chapel Hill, NC 27599-7280, USA. Tel: 919-966-0558. studies, based on the populations examined (including age ranges),
E-mail address: [email protected] (K.D. Allen). data sources, and different definitions of OA. A prior review

https://doi.org/10.1016/j.joca.2021.04.020
1063-4584/Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
 K.D. Allen et al. / Osteoarthritis and Cartilage 30 (2022) 184e195 185

Joint(s) Cohort/Data Source Country Age Group OA Definition(s) Findings

Any Joint
EPISER-2016 Spain 50 years Screening questions based on ACR  Weighted prevalence of self-
clinical criteria e hand, hip, knee or reported OA: 29.3% (weights
spine OA based on probability of selection
in each sampling stage)
Clinical Practice Research Datalink United Kingdom 20 years General practitioner diagnosis of  Age- and sex-standardized: 6.8
OA from electronic medical records cases of OA per 1000 person
years, prevalence of OA: 10.7%
Clinical Practice Research Datalink United Kingdom 45 years General practitioner diagnosis of  Annual age- and sex-adjusted
OA from electronic medical records rate for clinical OA: 29.2 per
1000 person years in 1992, 40.5
(95% CI 40.3, 40.7) per 1000
person years in 2013
Knee
Korean National Health and Korea 50 years KL Grade 2  Weighted prevalence of
Nutrition Examination Survey radiographic knee OA: 35.1%
(weights from sampling and
response rates and age/sex
proportions of 2005 Korean
National Census Registry)
Chingford Study (Women) United Kingdom 45e64 years Incident typical OA: KL 0 to 1, 0 to 2,  Cumulative 5-year incidence of
1 to 2 typical knee OA: 17.6%
Incident accelerated OA: KL 0 to 3  Cumulative 5-year incidence of
accelerated knee OA: 3.7%
EPISER-2016 Spain 40 years ACR clinical and radiological criteria  Weighted prevalence of
symptomatic knee OA: 13.8%
(weights based on probability of
selection in each sampling stage)
Clinical Assessment Study of the United Kingdom 50 years Radiographic evidence plus self-  Weighted prevalence of
Knee, Clinical Assessment Study of reported pain in the past 4 weeks radiographic, symptomatic knee
the Hand, and Clinical Assessment OA: 17.4% (weights accounted for
Study of the Foot initial selective non-response,
age, gender, and practice
location)
Hip
EPISER-2016 Spain 40 years ACR clinical and radiological criteria  Weighted prevalence of
symptomatic hip OA: 5.1%
(weights based on probability of
selection in each sampling stage)
Research on Osteoarthritis/ Japan 23 years KL Grade 2  Incidence rate of radiographic hip
osteoporosis Against Disability OA: 5.6 per 1,000 person years for
men and 8.4 per 1,000 person
years in women
Hand
Clinical Assessment Study of the United Kingdom 50 years Radiographic evidence plus self-  Weighted -prevalence of
Knee, Clinical Assessment Study of reported pain in the past 4 weeks radiographic, symptomatic hand
the Hand, and Clinical Assessment OA: 22.4% (weights accounted for
Study of the Foot initial selective non-response,
age, gender, and practice
location)
EPISER-2016 Spain 40 years ACR clinical criteria  Weighted prevalence of
symptomatic hand OA: 7.7%
(weights based on probability of
selection in each sampling stage)
Johnston County Osteoarthritis United States 45 years KL Grade 2 in at least one hand  Incidence of radiographic hand
Study joint OA (average 12-year period):
60.5%
 Incidence of symptomatic hand
OA (average 12-year period):
12.9%
Johnston County Osteoarthritis United States 45 years KL grade 2 in at least three total  Lifetime risk of symptomatic
Study joints in each hand (excluding hand OA: 39.8% (sampling
metacarpophalangeal (joints) and weights applied based on
at least one affected distal selection probability,
interphalangeal joint plus self- nonresponse adjustments, and
reported pain, aching or stiffness on post-stratification adjustment)
most days
Foot and
Ankle
Clinical Assessment Study of the United Kingdom 50 years KL Grade 2 plus pain in the same  Weighted radiographic,
Foot ankle symptomatic ankle OA: 3.4%
(weights accounted for initial
selective non-response)
(continued on next page)
186 K.D. Allen et al. / Osteoarthritis and Cartilage 30 (2022) 184e195

Table I (continued )

Joint(s) Cohort/Data Source Country Age Group OA Definition(s) Findings

Clinical Assessment Study of the United Kingdom 50 years Radiographic evidence plus self-  Weighted prevalence of
Knee, Clinical Assessment Study of reported pain in the past 4 weeks radiographic, symptomatic foot
the Hand, and Clinical Assessment OA: 16.5% (weights accounted for
Study of the Foot initial selective non-response,
age, gender, and practice
location)
Clinical Practice Research Datalink United Kingdom 20 years General practitioner diagnosis of  Age- and sex-standardized
OA from electronic medical records Incidence of ankle and foot OA:
0.2 per 1,000 person years
Johnston County Osteoarthritis United States 50 years Score of two or more for  Prevalence of radiographic foot
Project osteophytes or joint space OA: 22.1%
narrowing in at least one of five  Prevalence of symptomatic foot
joint sites plus foot pain on most OA: 5.3%
days of any month in the past 12
months
Johnston County Osteoarthritis United States 55 years Incident ankle OA: KL Grade 1 at  Incidence of radiographic ankle
Project follow-up among ankles with OA at 3.5 years: 28.2%
baseline KL Grade <1; Progressive  Progression of radiographic ankle
ankle OA: 1 KL Grade increase at OA at 3.5 years: 4.0%
follow-up among ankles with KL
Grade one at baseline

ACR ¼ American College of Rheumatology; KL¼ Kellgren Lawrence; OA ¼ osteoarthritis.

KL Grade 2 ¼ definite osteophytes and possible joint space narrowing.
ACR Clinical Criteria available here: https://www.rheumatology.org/Practice-Quality/Clinical-Support/Criteria.

FUNDAMENTALS OF OA Osteoarthritis and Cartilage

Table I
Results of recent (2017-present) cohort studies of the prevalence and incidence of OA

summarized prevalence and incidence data from studies of knee, There has also been interest in multiple-joint OA (MJOA), which
hip and hand OA data, illustrating this variability5. has been defined in at least 10 different ways12. Because of this
While most research has focused on OA at specific sites, some variability, it has been difficult to establish a consensus of the
studies have provided data on OA prevalence and incidence more prevalence of MJOA. A systematic review found prevalence esti-
generally. An estimated 240 million individuals worldwide have mates ranging from 5% to 25%13. Overall, MJOA has been associated
symptomatic OA, including 10% of men and 18% of women age 60 with poorer OA-related outcomes compared with single joint
and older6. Recent estimates from the Global Burden of Diseases, involvement.
Injuries and Risk Factors Study (GBD) found that globally, the age-
standardized point prevalence and annual incidence rate of Knee OA
symptomatic, radiographically confirmed hip and knee OA were
3754.2 (Uncertainty Index (UI) 3389.4e4187.6) and 181.2 (UI The prevalence and incidence of knee OA has been more
162.6e202.4) per 100,000, respectively; these represent 9.3% and widely studied than other joints2,3,9,14e18; data from recent
8.2% increases since 19907. Of note, GBD utilized available data studies are shown in Table I. The prevalence of symptomatic knee
sources on radiographic OA, and when data were not available for a OA has varied across studies. For example, among adults age 45
country, values were estimated based on similar countries and years in the US-based Framingham cohort, the prevalence of
territories, using disease-relevant country characteristics. Popula- symptomatic knee OA was 7%; in the US-based Johnston County
tion-based studies of OA prevalence and incidence have been Osteoarthritis project, the prevalence was 17%17,18. A recent meta-
conducted in multiple countries. In a large survey study of in- analysis found the overall pooled estimate of symptomatic knee
dividuals age 50 in England, about half of respondents indicated OA prevalence in China was 14.6%19. Using data from the National
having OA in at least one joint, including the hand, hip, knee and Health Interview Survey, along with a validated simulation model,
foot8. A recent survey study of individuals age 20 years in Spain an estimated 14 million people in the US have symptomatic knee
found that 29% of individuals (weighted prevalence) had OA at one OA20. Data from the Korean National Health and Nutrition Ex-
or more locations (including spine, hand, hip and knee), based on amination Survey (NHANES) reported the weighted prevalence of
screening questions corresponding to American College of Rheu- radiographic knee OA among adults age 50 years was 35.1%21.
matology (ACR) clinical criteria9. A United Kingdom (UK)-based Data from among individuals aged 60e74 years in the US NHANES
study, using a large nationally representative primary care data- showed that from 1974 to 1994, the age- and BMI-adjusted
base, found there were 494,716 incident cases of clinical OA be- prevalence of knee pain increased by approximately 65% in de-
tween 1997 and 2017, corresponding to 6.8 (95% Confidence mographic groups including non-Hispanic white and Mexican
Interval (CI) 6.7e6.9) per 1000 person years (age- and sex-stan- American individuals and African American women22. In the
dardized)10. Another study using this data source showed that Framingham Osteoarthritis Study, among adults aged 70 years,
among patients age 45 years, the annual age and sex-adjusted from 1983 to 2005, the age- and BMI-adjusted prevalence of knee
incidence rate for clinical OA increased from 29.2 (95% CI 28.8, 29.5) pain and symptomatic knee OA (but not radiographic knee OA)
to 40.5 (95% CI 40.3, 40.7) per 1000 person years from 1992 to approximately doubled among women and tripled among men22.
201311. Results from these two studies importantly suggest that increases
 K.D. Allen et al. / Osteoarthritis and Cartilage 30 (2022) 184e195 187

in the prevalence of knee pain and knee OA over time are not fully Foot & ankle
explained by increased rates of obesity. There has also been in-
terest in estimating the prevalence of patellofemoral OA specif- A recent systematic review of 18 studies found no true general
ically23. A meta-analysis including 85 studies found that about population prevalence estimates of radiographic ankle OA; preva-
half of individuals with knee pain or radiographic knee OA have lence estimates in various cohorts ranged widely from 0.0 to
patellofemoral involvement24. 97.1%37. Results of recent cohort studies are shown in Table I. The
Analyses from The Chingford Study found that the cumulative 5- Clinical Assessment Study of the Foot (CASF), including 5109 adults
year incidence of “typical” radiographic knee OA among women age 50 years in four UK based general practices, found the
age 45e64 years was 17.6%, and the incidence of “accelerated” weighted prevalence of ankle pain was 11.7% and symptomatic,
radiographic knee OA was 3.7%25. The lifetime risk of symptomatic radiographic ankle OA (grade2) was 3.4%37. In the Johnston
knee OA has been estimated to be between 14% and 45%, using County Osteoarthritis Project, 28% of adults age 55 years devel-
different cohorts and methodologies26,27. Another key study re- oped incident radiographic ankle OA over 3.5 years; among those
ported that the age- and sex-standardized incidence rate of with ankle OA at baseline, 4% had radiographic worsening38. In a
symptomatic knee OA among individuals in a community health UK-based study of a large nationally representative primary care
plan was 240 per 100,000 person years, rising substantially after database including adults age 20 years, the age- and sex-stan-
age 5028. dardized incidence of ankle and foot OA was 0.2 per 1,000 person
years10. A review of midfoot and forefoot OA found that most
Hip OA studies focused on radiographic OA, with wide variability in prev-
alence estimates (0.1e61%) based on age, gender and joint(s)
Recent cohort studies of the prevalence and incidence of hip OA studied39. The CASF study reported the weighted prevalence of
are shown in Table I. In a population-based study of adults age 40 symptomatic OA in the foot was 16.7%40 among adults age 50
years in Spain, the weighted prevalence of hip OA, based on ACR years, with 7.8% symptomatic OA in the first metatarsophalangeal
clinical and radiographic criteria, was 5.1%9. In the Framingham joint40 and 12.0% in the midfoot41. In the Johnston County Osteo-
cohort, the age-standardized prevalence of radiographic hip OA arthritis Project, among adults age 50 years the frequency of
among adults age 50 years was 19.6%, and the prevalence of radiographic foot OA was 22.1%, and symptomatic foot OA was less
symptomatic hip OA was 4.2%29. The prevalence of symptomatic common (5.3%)42,43. A community-based longitudinal cohort study
hip OA in the Johnston County Osteoarthritis Project (adults age of adults aged 40e91 years in Clearwater, Florida estimated a 25%
45 years) was higher, 10%30. Recent data from the Research on incidence of first metatarsophalangeal joint OA over an average of 7
Osteoarthritis/osteoporosis Against Disability cohort showed that years44.
the incidence rate of radiographic hip OA adults age 23 years was
5.6 per 1,000 person years for men and 8.4 per 1,000 person years in Person-level risk factors
women31. Among adults in a community health plan, the age- and
sex-standardized incidence rate of symptomatic hip OA was 88 per Table II presents key person-level risk factors for OA.
100,000 person years, rising substantially after age 5028. One US-
based study estimated that the weighted lifetime risk of symp- Demographic Characteristics
tomatic hip OA is 25%32.
Many studies have shown that OA risk increases with age and is
Hand greater among women compared with men2,3. Gender differences
in OA seem to be present across joint sites, with the potential
The prevalence of hand OA has been highly variable across
studies, with large differences between radiographic and
symptomatic disease, as well as based on different disease
definitions; results from recent cohort studies are shown in
Table I. In a study including three English cohorts age 50
Person-Level Factors Joint-Level Factors
years, the weighted prevalence of radiographic, symptomatic
hand OA was 22%, with first carpometacarpal joint OA being Age Joint Injury
Sex Joint malalignment (Mixed evidence)
the most common subtype15. In a Spanish study of adults age
Race/Ethnicity Joint Deformity/Abnormal Joint Shape
40 years, using ACR clinical criteria, the weighted prevalence Socioeconomic Status Muscle Weakness (Mixed evidence)
of hand OA was 7.7%9. Earlier research from the Framingham Rural Residence Leg length Inequality
Osteoarthritis study reported the age-standardized prevalence Family History and Physically Demanding Occupational Tasks
of symptomatic hand OA was 14% in women and 7% in men33; Genetic Factors
Obesity Elite sports
this increased to 26% and 13% among those age 71 and older in
High Blood Pressure
the Framingham cohort34. (Mixed evidence)
In the US-based Johnston County Osteoarthritis Project, the High Bone Mineral Density
incidence of radiographic hand OA among adults age 45 years Metformin Use
was 60%, and the incidence of symptomatic hand OA was 13% over
a 12-year average follow-up period35. In the same cohort, the
weighted lifetime risk of symptomatic hand OA was 40%36. In the Table II Osteoarthritis and Cartilage
Framingham Osteoarthritis study, the 9-year incidence of radio-
graphic hand OA at any joint was about 35%, with an incidence of FUNDAMENTALS OF OA
symptomatic hand OA (at one or more joints) being 4% in men and
10% in women33. Among adults in a community health plan, the Person- and joint-level factors with evidence for impacting risk for
age- and sex-standardized incidence rate of symptomatic hand OA developing OA
was 100 per 100,000 person years, rising substantially after age
5028.
188 K.D. Allen et al. / Osteoarthritis and Cartilage 30 (2022) 184e195

exception of cervical spine OA2. Racial and ethnic differences are associated with better physical function74. Earlier work also sug-
also well documented45. In the US, multiple studies have found that gested a potential role of low vitamin K with OA risk and pro-
Blacks have greater prevalence and severity of lower extremity OA gression3. There has been conflicting evidence regarding potential
than Whites45. A recent study of the Osteoarthritis Initiative cohort roles of vitamins C and E with OA risk and progression3.
found that Black participants had lower odds of radiographic In addition to research on specific vitamins, other studies have
(OR ¼ 0.79, 95% CI 0.66, 0.94) and symptomatic (OR ¼ 0.63, 95%CI examined the association of various types of diets with OA. There is
0.49, 0.82) hand OA compared to Whites; however, it should be some evidence for a positive influence of higher dietary fiber, soy
noted that this cohort includes only individuals with or at risk for milk intake, and Mediterranean diet on various OA outcomes, but
knee OA46. Studies have observed that Chinese women have about additional studies are needed to confirm these findings3.
45% higher prevalence of radiographic and symptomatic knee OA
than white women, with no difference between Chinese and white Bone density and bone mass
men47,48. However, hip OA is less common among Chinese in-
dividuals, compared with whites49. Studies from multiple countries Multiple studies have found that higher bone mineral density is
have shown that OA prevalence, particularly at the knee and hip, is associated with greater risk for radiographic knee and hip
higher among individuals with lower socioeconomic status, as well OA2,3,75e77. A recent Mendelian randomization study using UK
as in rural communities45. Biobank data found evidence for a causal relationship of high
femoral neck bone mineral density with all OA, knee OA and hip
Obesity and metabolic and inflammatory factors OA; methods applied in this study provide strong support that the
association of bone mineral density and OA risk is not due to
The associations of obesity and metabolic syndrome with OA collider bias78. Another study identified an association of bone
have continued to be a major research focus50e54. There is a clear mineral density with hip and knee replacements79. Although most
association of overweight with increased risk for OA, particularly at studies have not observed an association with high bone mineral
the knee; one systematic review found that obesity increased the density with OA progression75, a recent study found that high bone
risk of OA about 3-fold2,3,55,56. A systematic review found no as- mass was associated with progression of osteophytes79, but only
sociation of metabolic syndrome with hip OA, insufficient evidence when combining incidence and progression outcomes.
for hand OA, and no significant association with knee OA in studies
that controlled for weight57. However, there have been mixed re- Other person-level factors
sults in other studies. One recent study reported that metabolic
syndrome and low high density lipoprotein levels were associated Some studies have found that smoking confers a small protec-
with medial compartment cartilage volume loss and bone marrow tive effect for the development of radiographic knee and hip (but
lesion size increase, even when controlling for body mass index; not hand) OA80,81, though findings have not been consistent82.
however, some individual components of metabolic syndrome Studies have also evaluated the association of statin use with OA,
were not associated with these changes, and there were no sig- and a recent meta-analysis found no significant relationship with
nificant associations for lateral compartment OA58. There is also OA incidence or progression83. However, there have been some
some evidence that some components of metabolic syndrome are promising data regarding the potential role of metformin in
associated with greater knee pain59e61. One potential pathway reducing OA risk and progression. For example, in the Osteoarthritis
linking obesity and metabolic syndrome with OA outcomes is Initiative, medial cartilage volume loss was lower in metformin
inflammation. Several recent studies have identified associations of users than non-users, with a difference of 0.86% (95% CI
inflammatory factors (e.g., resistin, interleukin-8, S100A8/S100A9) -1.58%, 0.15%) per year after adjustment for key covariates;
with knee OA some aspects of knee OA severity and symptoms; however, there was no relationship of metformin with lateral
however, results have been mixed, with one study finding no as- compartment cartilage volume loss or change in symptoms84. Some
sociation of interleukin-8 with non-weight-bearing pain, for studies found an association of blood pressure with OA, including a
example62,63. recent analysis of Osteoarthritis Initiative data that observed a
correlation between higher diastolic blood pressure and increased
Vitamin and nutritional factors cartilage matrix degenerative changes over time85. However, other
research has failed to observe an association between blood pres-
The role of specific vitamins and diet also continues to be an sure and OA51. There has been evidence for an association of low
active research area. Vitamin D has been the most extensively birth weight with hip and knee OA3. Studies have examined asso-
studied, including epidemiological studies and trials of supple- ciations of various environmental pollutants with OA, with poten-
mentation. Findings of these studies have been conflicting64,65. tial positive relationships for lead and organic pollutants including
Three trials of vitamin D supplementation failed to find effects on polychlorinated biphenyls86,87.
structural or symptomatic outcomes66e68, though there has some
indication that participants who consistently maintain sufficient Joint risk factors
25-hydroxyvitamin D levels had better outcomes69. Recent data
from the Osteoarthritis Initiative cohort indicates greater vitamin D Table II presents key joint-level risk factors for OA.
level was associated with some metrics of better knee cartilage
architecture on MRI, as well as less progression of joint abnor- Bone/joint shape
malities; however, vitamin D level was not associated with all
components of cartilage health and joint progression examined in Variation in bone/joint shape previously has been linked with
these studies70,71. Other research indicates that among individuals OA at the hip and knee2,88, and more recent cohort studies have
with knee OA, vitamin D supplementation may positively impact added to our understanding of the relationship at these joints. In a
depressive symptoms and foot pain72,73. Vitamins D and K may nested caseecontrol study using Johnston County Osteoarthritis
also be important in combination; among participants in the Project data, compared to control hips, hips with moderate radio-
Health, Aging and Body Composition Study and Osteoarthritis graphic OA (KellgreneLawrence grade 3) were more likely to have
Initiative, sufficient levels of both vitamin D and vitamin K were cam morphology (abnormality of the femoral headeneck junction
 K.D. Allen et al. / Osteoarthritis and Cartilage 30 (2022) 184e195 189

linked to femoroacetabular impingement) in both men and women Osteoarthritis Project, Multicenter Osteoarthritis Study, and Oste-
and to have protrusio acetabuli (acetabulur overcoverage defect) oarthritis Initiative between limb length inequality and preva-
only in women89. In the Rotterdam Study, cam deformity and lent3,105, incident105,106, and progressive radiographic hip OA106.
acetabular dysplasia were independent risk factors for incident Radiographic OA in the knee and hip may be more common in the
radiographic hip OA (mean follow up 9.2 years)90. Data from the shorter limb3,105.
Chingford Study, the Johnston County Osteoarthritis Project, and
Beijing Osteoarthritis Study showed variation by race in hip joint Muscle strength, mass, and quality
morphological characteristics related to hip OA. Compared to hips
from European Caucasians, American Caucasians, and African Several recent studies and reviews have examined the role of
Americans, hips from Chinese individuals were less likely to have muscle strength in knee OA. A systematic review and meta-analysis
hip morphology features commonly seen in hip OA91, which is of 27 studies found low quality evidence that adults with medial
consistent with a prior study showing that morphological differ- and/or lateral knee OA had 4.0 (95%CI 2.7, 6.0) times the odds of
ences associated with hip OA (i.e., femoral head asphericity) were having knee extensor muscle weakness compared to adults
less common in Chinese than Caucasian individuals92. For the knee, without knee OA, while nine studies indicated that adults with
data from the Osteoarthritis Initiative showed varying mediation knee OA had 4.1 (95%CI 1.5, 11.3) times the odds of having knee
effects between sex and incident knee OA for two tibial modes flexor weakness107. A meta-analysis of five studies (5700 partici-
(distinct joint shapes) and one distal femoral mode that reflect the pants) found that men and women with knee extensor muscle
relative angles of the heads to the shafts of the femur and tibia93. In weakness had 1.7 (95%CI 1.2, 2.2) times the odds of developing knee
a caseecontrol study nested in the Osteoarthritis Initiative, specific OA over the next 2.5e14 years108. A subsequent meta-analysis of 15
baseline morphological features of the proximal tibiofemoral joint studies (>8000 participants) found that lower knee extension
T2-weighted MRI (i.e., greater contact area, load-bearing area and strength was associated with increased risk for worsening knee
posterior stress-bolstering area) were associated with incident symptoms and function over the next 1.5e8 years109. They did not
radiographic knee OA, predominantly in the medial compart- observe increased risk for structural deterioration. Recent studies
ment94. A recent extensive genetic epidemiology review suggests continue to show variable associations of thigh strength with the
specific genes are linked to both joint shape and OA, including development and progression of knee OA. A series of studies by
Growth Differentiating Factor 5, SOX9, Parathyroid hormone-like Culvenor and colleagues observed that knee extensor and flexor
hormone, Collagen type XI, and Astrotactin 295. weakness was associated incident radiographic OA in women but
not men, and with radiographic OA progression in men but not
Injury and surgery women110e112. However, other studies observed that knee extensor
weakness was not associated with OA progression in both men and
Prior traumatic joint injury and subsequent surgery are potent women99,113. Further, knee extensor and flexor strength loss was
risk factors for OA. Most evidence for post-traumatic OA exists for associated with symptomatic progression in women112. Poor
the knee. An updated systematic review and meta-analysis found muscle quality, including increased intramuscular fat, was associ-
that the odds for knee OA were 4.2 (95%CI 2.2, 8.0) times as high ated with radiographic OA progression and greater cartilage vol-
after isolated anterior cruciate ligament (ACL) injury, 6.3 (95%CI 3.8, ume loss112.
10.5) times as high after isolated meniscus injury, and 6.4 (95%CI
4.9, 8.3) times as high for those after combined ACL and meniscus Joint alignment and loads
injury compared to the uninjured knee96. There is growing evi-
dence that increased risk for post-traumatic OA extends to the Static joint alignment, particularly frontal plane knee alignment,
patellofemoral joint, in addition to the tibiofemoral joint97. In older is a strong, well-established predictor of knee OA progression2,3.
adults, a recent knee injury is a risk factor for the accelerated Consistent with the syntheses of prior work2,3, new data regarding
development of knee OA98. However, there is strong evidence that the association of static alignment with prevalent or incident knee
prior knee injury is not associated with radiographic OA progres- OA remains mixed. A meta-analysis observed that adults with
sion99. In other joints where idiopathic OA is rare, such as the elbow prevalent knee OA have similar odds of valgus and varus mala-
or ankle, cases of OA are often attributable to prior joint lignment as adults without OA107. However, a more recent popu-
injury100,101. However, more high-quality research is needed to lation-based longitudinal study in rural China found that varus
further understand post-traumatic OA at other joints. malalignment was associated with prevalent medial knee OA and
Evidence regarding surgery alone as a risk factor for knee OA is valgus malalignment was associated with prevalent lateral knee
mixed. Data from observational cohorts suggest that surgery via OA114. Among knees with varus malalignment, increased coronal
arthroscopic meniscectomy is a risk factor for incident radiographic tibial slope was associated with incident accelerated knee OA in a
knee OA and OA progression102, particularly in those without a caseecontrol study115. In the patellofemoral joint, patellofemoral
history of knee trauma103. In contrast, results from a recent ran- malalignment and trochlear morphology were associated with
domized controlled trial found that adults with degenerative incident patellofemoral osteophytes 1 year after ACL reconstruc-
meniscal tears who received surgery (i.e., arthroscopic partial tion; however the effect size was small116.
meniscectomy) did not have higher risk for developing radio- Regarding dynamic alignment and knee loading, altered knee
graphic OA compared to adults who received no surgery (i.e., ex- joint loading during walking is consistently observed in adults with
ercise therapy only)104. medial knee OA. A meta-analysis of 10 studies of moderate quality
found that adults with medial knee OA had 3.0 (95%CI 1.9, 4.9)
Limb length inequality times the odds of demonstrating a higher adduction moment while
walking compared to adults without knee OA107.
Previous analyses from the Johnston County Osteoarthritis
Project and the Multicenter Osteoarthritis Study demonstrated Occupation and physical activity
associations between limb length inequality and prevalent radio-
graphic, incident symptomatic, and progressive radiographic knee Physically demanding occupations are associated with
OA3. For the hip, associations were observed in the Johnston County increased risk for OA2,3. In a recent systematic review, physically
190 K.D. Allen et al. / Osteoarthritis and Cartilage 30 (2022) 184e195

demanding occupations including construction workers, floor sensitization, psychological distress, radiographic severity, body
layers, brick layers, fishermen, farmers, and service personnel were mass index, muscle strength, inflammation and comorbidities are
associated with a higher risk for hip and knee OA117. In some oc- associated with clinically distinct phenotypes; gender, obesity,
cupations, a doseeresponse relationship existed. For example, metabolic abnormalities, pattern of cartilage damage, and inflam-
farmers who reported over 5 h of work in an animal barn had a mation may be important factors with respect to structural phe-
higher risk of OA compared to farmers with <5 h117. The review also notypes128. Another review identified six main phenotypes: 1)
identified occupational tasks associated with risk for developing chronic pain in which central mechanisms are prominent; 2) in-
hip or knee OA, including lifting and carrying, kneeling with or flammatory; 3) metabolic syndrome; 4) bone and cartilage meta-
without squatting, climbing, standing, crawling, walking, and bolism; (5) mechanical overload/varus malalignment; 6) minimal
higher overall physical load117. joint disease127; a recent study classified 84% of Osteoarthritis
Participating in physical activity is generally not associated with Initiative participants based on these subgroups, with 20% having
OA and may even reduce the risk for OA. In one study, adults who overlap across subgroups129. Because approaches to studying OA
participated in moderate levels of pedometer-based physical ac- phenotypes have varied markedly, an international group of re-
tivity had less risk for knee osteophyte progression compared to searchers recently led an effort to develop consensus-based defi-
those with low level of physical activity118. However, risk for OA is nitions and recommendations that create a common framework for
elevated for those who participated in certain sports. A systematic conducting and reporting OA phenotype research130.
review of studies investigating runners found that prevalence of
hip and/or knee OA was lower in recreational compared to Conclusion
competitive runners and non-runners119. Further, competitive
runners had greater odds of OA compared to recreational runners, Studies across the world have continued to illustrate the high
but the odds were not higher than non-runners. In addition to prevalence and negative impacts of OA, with a disproportionate
competitive distance running, another systematic review found burden among some racial/ethnic groups and individuals with
that participation in recreational and competitive soccer, compet- lower socioeconomic status. The most established modifiable per-
itive weight lifting, and wrestling were associated with knee OA120. son-level risk factor for OA is clearly obesity, highlighting the
Taken together, these data suggest a potential U-shape relationship importance of research, clinical, and public health efforts aimed at
where insufficient physical activity and frequent, highly-intensive successful weight loss and weight maintenance interventions. At
physical activity both associated with OA, though further research the joint-level, the clearest modifiable risk factor is injury. This
is needed, particularly for hip OA, which has been less studied. supports the need for continuing efforts to both reduce injury risk,
particularly sport-related ACL tears, and understand the pathway
Other joint-level factors from injury to OA in order to develop interventions that can disrupt
this trajectory. Gaps remain in our understanding of OA epidemi-
Multiple recent analyses of data from the Osteoarthritis ology. There are limited data on the prevalence and incidence of
Initiative have elucidated the role of MRI features in the prediction spine OA, and varying OA definitions (particularly for the hand)
of OA. T2 relaxation times on MRI (changes in collagen integrity create challenges when comparing across cohorts. The role of some
and cartilage water content) were associated with radiographic potential risk factors (e.g., specific diets, some vitamins, blood
knee OA at 2 years and total knee replacement at 5 years, sug- pressure, joint surgery, muscle strength, static joint alignment) is
gesting that this measure may be an early biomarker in the still unclear, and additional rigorous studies are still needed. Finally,
diagnosis and prediction of OA121. Certain characteristics of there continues to be recognition and study of the heterogenous
meniscal shape predicted knee OA progression at 24 months, nature of OA. This calls for more complex study designs and ana-
including a larger meniscal longitudinal diameter, larger meniscal lyses that consider interrelationships among multiple risk factors,
width, and smaller meniscal angle122. Infrapatellar fat pad signal as well as continued exploration of phenotypic definitions that help
intensity alterations were associated with incident radiographic to define patterns of OA.
knee OA over 4 years123, as well as incident knee replacement
over 5 years among participants with baseline knee OA124. Addi-
Contributions
tionally, higher signal intensity of the infrapatellar fat pad was
related to progression of knee OA on MRI over 2 years, as noted by
KDA, LMT and YMG contributed to the conception and design of the
greater loss of tibial cartilage volume, larger increases in tibiofe-
review and interpretation of data, drafted the article and revised it
moral cartilage defects, and increases in tibiofemoral bone
critically for important intellectual content, and approved the final
marrow lesions125. Periarticular bone measures (i.e., higher
version of the manuscript to be submitted.
medial:lateral ratio, greater bone volume fracture, trabecular
thickness and number, lower trabecular spacing) were strongly
related to progression of radiographic medial tibiofemoral joint Funding source
space narrowing over 12 months126. KDA and YMG receive support from the National Institute of
Arthritis and Musculoskeletal and Skin Diseases Core Center for
Phenotypes Clinical Research at the University of North Carolina, Chapel Hill
(P30AR072580). KDA receives support from a VA Health Services
There is great interest in understanding and defining OA phe- Research and Development Research Career Scientist Award (19-
notypes that involve combinations of disease characteristics. A 332) and the Center of Innovation to Accelerate Discovery and
major motivation underlying this research is the identification of Practice Transformation (ADAPT) (CIN 13-410) at the Durham VA
subgroups of patients who may respond differently to treatment Health Care System.
strategies, thereby enhancing the personalization and effectiveness
of care. Prior reviews summarized the literature on OA phenotypes Conflict of Interest
in depth127,128. These studies included clinical, laboratory and im-
aging phenotypes and varied considerably in the variables The authors have no competing interests to declare regarding this
included128. One systematic review found evidence that pain manuscript.
 K.D. Allen et al. / Osteoarthritis and Cartilage 30 (2022) 184e195 191

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