Epidemiology of Pain in Osteoarthritis

Pain is the most prominent symptom of OA and most often is the reason patients seek medical help.
Although subjective, OA pain can be measured and is presently the best criterion for evaluating
potential therapies. In OA of the knee, pain may be caused primarily by mechanical and chemical
stimuli.[5] Possible sources of pain in patients with OA include the synovial membrane, joint capsule,
periarticular ligaments, periarticular muscle spasm, periosteum, and subchondral bone.[6] Bone-related
causes of pain include periostitis associated with osteophyte formation, subchondral microfractures,
bone angina due to decreased blood flow and elevated intraosseous pressure, and bone marrow lesions
detected on magnetic resonance imaging (MRI). Synovial causes of pain include irritation of sensory
nerve endings within the synovium from osteophytes and synovial inflammation that is due, at least in
part, to the release of prostaglandins, leukotrienes, and cytokines.

Radiographically, patients with OA may exhibit osteophytes, periarticular ossicles, narrowing of joint
space, subchondral cysts and sclerosis, bony attrition, and sharpening of the tibial spine.[4,7] The global
system of Kellgren and Lawrence, developed for use in epidemiologic studies, comprises a 5-point scale
for grading radiographs of osteoarthritic joints, in which 0 = no changes; 1 = doubtful joint space
narrowing; 2 = minimal change, mostly characterized by osteophytes; 3 = moderate change,
characterized by multiple osteophytes and/or definite joint space narrowing; and 4 = severe change,
characterized by marked joint space narrowing with bone-on-bone contact with large osteophytes
(Figure 1).[7,8] Although still used, this system was based on nonweight-bearing X rays, whereas
weight-bearing films are currently considered standard for grading in the clinical setting.[9]

As noted by Altman et al,[4] radiographic tibiofemoral knee OA is defined as joint space narrowing,
marginal osteophytes, subchondral sclerosis, malalignment, bony attrition, and hypertrophy of tibial
spines. Patellofemoral knee OA is defined as joint space narrowing, marginal osteophytes, subchondral
sclerosis, and subluxation.

Figure 1a. Radiographs of knee osteoarthritis. Grade 1: Doubtful narrowing of joint space and possible
osteophytic lipping.

Figure 1b. Grade 2: Definite osteophytes and possible narrowing of joint space.

Figure 1c. Grade 3: Moderate multiple osteophytes, definite narrowing of joint space and some
sclerosis, and possible deformity of bone ends.

Figure 1d. Grade 4: Large osteophytes, marked narrowing of joint space, severe sclerosis, and definite
deformity of bone ends. Reprinted with permission from Kellgren JH. Atlas of Standard Radiographs of
Arthritis. 2nd ed. Philadelphia, Pa: FA Davis Co; 1963:1-13.
Pain and Radiographic Studies

Several studies have demonstrated the correlation between radiographic features of knee OA and the
presence and severity of knee pain.

NHANES-1 examined factors associated with knee pain in 6913 people who underwent nonweight-
bearing radiographs of both knees. Pain was reported by 39% of participants with grade 2 changes in OA
and 61% of those with grade 3 or 4 changes.[10]

In the Baltimore Longitudinal Study of Aging, 675 people underwent weight-bearing radiographs of both
knees. Only 9.4% to 14.4% of grade 0 participants reported current knee pain, whereas 11.8% to 21.9%
of grade 1 participants, 20.4% to 29.9% of grade 2 participants, 53.8% to 64.1% of grade 3 participants,
and all of the grade 4 participants reported pain. Osteophyte formation, joint space narrowing, and
subchondral sclerosis were associated with reports of pain.[11]

Two population-based studies, the Michigan Bone Health Study and the Study of Women's Health
Across the Nation, evaluated weight-bearing radiographs of both knees of 829 premenopausal and
perimenopausal women aged 40 to 53 years.[12] It was found that 23.2% of black women had
radiographic evidence of OA (defined as grade 2 or higher) and 29.4% reported knee pain, whereas 8.5%
of white women had radiographic evidence of OA and 19.2% reported knee pain. Joint pain in black
women was more likely than was that in white women to be associated with radiographic OA of the
knee.

Creamer et al[13] evaluated pain severity, disability, and psychosocial variables among 68 outpatients
with clinical diagnoses of knee OA and current knee pain. Anteroposterior radiographs of the
tibiofemoral joints were reviewed, as were lateral patellofemoral radiographs. The factors that
correlated with pain severity included higher body mass index, lower educational level, feelings of
helplessness, and poor self-efficacy. Pain threshold or physical examination findings did not correlate
with pain severity, but total osteophyte score did correlate with pain (P = .01). Joint space narrowing
and subchondral sclerosis were not associated with pain severity. Disability was associated with higher
levels of pain; higher body mass index; feelings of anxiety, fatigue, and helplessness; and lower levels of
education, self-efficacy, and quality of life.

Finally, in the Johnston County Osteoarthritis Project, Jordan and colleagues[14] reported that persons
45 years and older with moderate to severe knee pain had higher adjusted mean Health Assessment
Questionnaire scores independent of radiographic knee OA. Mild knee pain, however, was associated
with higher adjusted mean questionnaire scores only in obese participants with radiographic knee OA.