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f1-tcrm-7-393: Treatment algorithm for symptomatic osteoarthritis.Abbreviations: COX-

2, cyclo-oxygenase-2; IV, intravenous; NSAID, nonsteroidal anti-inflammatory drug;
PGE2, prostaglandin E2; PPI, proton pump inhibitor; PO, oral; SNRI, selective
norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.

Mentions: Osteoarthritis affects many older persons aged ≥65 years. Knee osteoarthritis
occurs in more than 32% of these individuals,1 and hand osteoarthritis occurs in more
than 50% of older patients.2 A multitude of treatment modalities are available for patients
with osteoarthritis, among which a balance between efficacy, safety, and convenience
must be found to achieve successful long-term management of symptoms. An algorithm
has been proposed as an aid to navigating the clinical options (see Figure 1).3
Acute Knee Injuries: Use of Decision
Rules for Selective Radiograph
Ordering
HOWARD B. TANDETER, M.D., and PESACH SHVARTZMAN, M.D., Ben-Gurion
University of the Negev, Beer-Sheva, Israel

MAX A. STEVENS, M.D., University of Iowa Hospitals and Clinics, Iowa City, Iowa

Am Fam Physician. 1999 Dec 1;60(9):2599-2608.

Family physicians often encounter patients with acute knee trauma. Radiographs of
injured knees are commonly ordered, even though fractures are found in only 6 percent of
such patients and emergency department physicians can usually discriminate clinically
between fracture and nonfracture. Decision rules have been developed to reduce the
unnecessary use of radiologic studies in patients with acute knee injury. The Ottawa knee
rules and the Pittsburgh decision rules are the latest guidelines for the selective use of
radiographs in knee trauma. Application of these rules may lead to a more efficient
evaluation of knee injuries and a reduction in health costs without an increase in adverse
outcomes.

Family physicians are frequently called on to evaluate patients who have acute knee
injuries.1 Each year, knee trauma is also responsible for an estimated 1.3 million visits to
emergency departments in the United States.2 The anatomic characteristics of the knee,
its exposure to external forces and the functional demands placed on the joint may
explain the frequency of injury.

Standard emergency medicine textbooks imply that radiographs should be routinely

obtained for every patient who presents with a knee injury.3–5 Consequently, radiographs
are among the most commonly ordered imaging studies for traumatic injury to the knee
joint.6,7 This situation persists despite the absence of clear supporting data and the fact
that only 6 percent of patients with knee trauma have a fracture.6–9

Even though emergency department physicians can discriminate clinically between

fracture and nonfracture, they order radiographs for most patients with acute knee injury.
Reasons for the unnecessary use of radiography include fear of lawsuits, failure to obtain
an adequate history and expectations on the part of patients.10–12

Overuse of radiologic studies has become a significant economic problem in the United
States.11,13 Although knee radiographs are relatively inexpensive, high volume of a low-
cost test has the same overall financial impact as low volume of a high-cost
procedure.14,15 Unnecessary radiation exposure and prolonged waiting times are other
reasons to decrease the use of radiologic studies. The application of decision rules for the
selective ordering of radiographs may result in a more efficient evaluation of patients
with acute knee injuries and may reduce the use of radiography in these patients.

This article briefly reviews the anatomy of the knee joint as well as the most common
knee fractures and ligament injuries. Clinical decision rules for ordering diagnostic
radiographs following knee injuries are also discussed, with special emphasis given to the
guidelines developed in Ottawa, Ontario, and Pittsburgh, along with their potential use in
the management of knee injuries.

Anatomy of the Knee

The anatomy and function of the knee are quite complex, and only the basics are
described in this article. The osseous structures of the knee include the distal femoral
condyles, proximal tibial plateau and patella (Figure 1). The tibial plateau articulates with
the femoral condyles, and the patellofemoral groove (located anteriorly between the
femoral condyles) accepts the patella. The tibia and patella do not articulate. The gliding
motion of the patella across the femur allows smooth extension at the knee and increases
the mechanical advantage of the quadriceps.

FIGURE 1.

Anterior view of the osseous, ligamentous and fibrocartilaginous structures of the knee.
View Large

The extra-articular muscle-tendon units include the quadriceps and patellar tendons
(responsible for knee extension), medial and lateral hamstrings (chiefly responsible for
knee flexion), gastrocnemius muscle, popliteal ligament and iliotibial band (Figure 2).

FIGURE 2.

Anterior and posterior views of the extra-articular tendinous structures and muscles
associated with the knee.

View Large

The extra-articular ligamentous structures include the tibial and fibular collateral
ligaments (Figure 1). These ligaments act as the principal extra-articular static stabilizing
structures (i.e., they provide stability for the medial and lateral aspects of the knee).

The intra-articular structures include the medial and lateral menisci and the anterior and
posterior cruciate ligaments (Figure 1). The menisci are fibrocartilaginous wedges that
rim and cushion each tibiofemoral articulation. The anterior and posterior cruciate
ligaments provide stability for the knee joint.

Knee Fractures
Fractures may occur in the patella, femoral condyles or tibial plateau.16 Patellar fractures
are divided into transverse, vertical, upper pole, lower pole, comminuted and
osteochondral fractures (Figure 3). Each type can be undisplaced or displaced (Figure 4).
The two main mechanisms of patellar fracture are direct trauma to the anterior aspect of
the knee or a powerful contraction of the quadriceps muscle (transverse, upper pole and
lower pole fractures).

FIGURE 3.

Fractures of the patella. This bone can be fractured through one of its poles or through its
central body. Patellar fractures can be simple or comminuted.

View Large

FIGURE 4.

Displaced fracture of the lower pole of the patella (arrow).

View Large

Radiographs are essential to assess traumatic patellar injury. In addition to antero-

posterior, notch and lateral views, Merchant and infrapatellar views with the knee in 45
degrees of flexion may be necessary to identify an osteochondral fragment (Figure 5).

FIGURE 5.

Osteochondral fragment (bottom arrow), which represents a small fracture of the patella
with hemarthrosis. A fluid collection is also seen (top arrow).

View Large

Fractures of the femoral condyles involve the distal 9 to 15 cm of the femur (Figure 6).
Both the diaphyseal and metaphyseal regions may be involved. Fractures may also show
intra-articular extension. Most condylar fractures occur as a result of motor vehicle
accidents. Other causes include falling on a flexed knee or falling from a height. In young
people, higher energy is necessary for a fracture to occur; consequently, more soft tissue
damage is also present. In older patients with osteoporosis, less energy is needed to
produce a fracture; therefore, less associated soft tissue damage is present.

FIGURE 6.
Oblique view of a lateral femoral condyle fracture that extends to the articular surface
(arrows).

View Large

Fractures of the tibial plateau are of special importance because they occur in one of the
most important weight-bearing areas (Figure 7). These fractures may involve the
metaphysis, epiphysis and/or articular cartilage. The forces that produce fractures in this
area are compression, valgus force (outward twisting [away from the midline]) or a
combination of both. The fractures primarily involve the lateral plateau, the medial
plateau or both structures (bicondylar fractures).
FIGURE 7.

Fractures of the tibial plateau. These fractures can be comminuted (top) or can be limited
to the depression of the tibial plateau, or they can also involve the displacement of both
plateaus and can be associated with fibular head fracture (bottom).
View Large

Knee Ligament Injuries

No validated rules have been formulated for the use of radiography in patients with
suspected ligament injuries, but a decision tree can be used as a guide (Figure 8).17
Although plain radiographs may be useful in the initial diagnosis of these injuries,
magnetic resonance imaging (MRI) is becoming the preferred diagnostic method18 and is
rapidly replacing other techniques as the study of choice for the evaluation of knee
injuries.19 However, the routine use of MRI has been questioned because of its
significant cost ($600 to $1,200) and the high accuracy of clinical examination in
diagnosing some injuries.20

Evaluation of Collateral Ligament Injury

FIGURE 8.

Suggested decision tree for the evaluation of collateral ligament injury. (RICE = rest, ice,
compression and elevation)

Adapted with permission from Smith BW, Green GA. Acute knee injuries: Part II.
Diagnosis and management. Am Fam Physician 1995;51:800.

View Large

ANTERIOR CRUCIATE LIGAMENT

Rupture of the anterior cruciate ligament (ACL) is a serious injury, and the diagnosis may
be missed.18 This type of injury can be produced by pure hyperextension or by a
combination of valgus force and external rotation of the tibia relative to the femur.

The immediate development of a hemorrhagic effusion is an important point in the

history of ACL injury (Figure 9). The stability of the ACL may be clinically assessed with
the use of the Lachman test (modified anterior drawer test). More than 90 percent of ACL
injuries can be detected based on the history and physical examination.17 However, even
the best specialists may fail to recognize the joint laxity of an ACL injury. Therefore,
radiographic signs are useful in making the diagnosis.

FIGURE 9.

Fluid level (arrows) seen on a cross-table lateral radiograph. This indicates the presence
of hemarthrosis from injury of the anterior cruciate ligament.

View Large

ACL injury has three main radiographic signs: (1) avulsion of the intercondylar tubercle
(Figure 10), (2) anterior displacement of the tibia with respect to the femur, termed the
“radiographic drawer sign,” and (3) Segond fracture (a thin sliver of bone avulsed from
the proximal lateral tibia with the lateral capsular ligament), termed the “lateral capsular
sign”16 (Figure 11). Note, however, that these radiographic signs are frequently absent in
patients with ACL injuries.

FIGURE 10.

Avulsion of the intercondylar tubercle (arrow), indicating injury of the anterior cruciate
ligament.

View Large

FIGURE 11.

Segond fracture (arrow), which is a cortical avulsion of the proximal lateral tibial plateau
that also involves the lateral capsule.

View Large

The gold standard for the diagnosis of ruptured ACL is arthroscopy. Compared with this
procedure, MRI has a diagnostic accuracy of more than 90 percent. In addition,
ultrasound examination has been shown to be a useful and inexpensive mode of detecting
a ruptured ACL in the clinical setting of a traumatic hemarthrosis.21

POSTERIOR CRUCIATE LIGAMENT

Injuries of the posterior cruciate ligament (PCL) are relatively uncommon, apparently
because this is the strongest major knee ligament. The mechanism of isolated PCL injury
is blunt trauma to the anterior proximal tibia (“dashboard injury”).
Several maneuvers can be helpful in diagnosing PCL injuries (Figure 12). In one study,22
the gravity sign near extension correctly diagnosed PCL injury in 20 of 24 patients, and
active reduction of posterior tibial subluxation correctly identified PCL injury in 18 of 24
patients. The gravity test is performed at 20 degrees of knee flexion. Neither maneuver
requires anesthesia.

FIGURE 12.

Two maneuvers to detect posterior cruciate ligament injury. (A) Gravity sign near
extension test. In a resting position with the distal femur on a 15-cm support and the heel
resting on the examination table (20 degrees of flexion), the unsupported proximal tibia
displays a concave anterior contour. (B) Active reduction of posterior tibial subluxation.
When the patient raises the heel 2 to 3 cm, a normal anterior contour is restored.

View Large

Nonetheless, clinical diagnosis may be difficult, and radiographic signs are important.18
The most common radiographic sign of PCL injury is avulsion at the site of the ligament's
origin on the posterior tibia (Figure 13). Less commonly, avulsion can be seen at the site
of PCL insertion at the medial femoral condyle. When the PCL fails, posterior sagging of
the tibia relative to the femur may be seen on the lateral radiograph.
FIGURE 13.

Avulsion at the site of origin on the posterior tibia (arrow), resulting from injury of the
posterior cruciate ligament.

View Large

MRI is accurate in diagnosing PCL injuries. It can also show associated injuries of the
ACL and medial collateral ligament (MCL), as well as bone contusions.

MEDIAL COLLATERAL LIGAMENT

Knee injuries involving valgus force, with or without a rotational element, are suggestive
of MCL injury. The physical examination may demonstrate effusion or local soft tissue
swelling and ecchymosis.18 Injuries to the MCL usually occur at the ligament's proximal
origin. Therefore, tenderness is usually localized along the distal femur and extends to the
joint line.17

The major secondary radiographic sign of MCL injury is widening of the medial joint
space. A lateral tibial plateau fracture may also suggest MCL injury.

MRI demonstrates MCL injury as well as associated injuries of the medial meniscus,
capsule and ACL.

LATERAL COLLATERAL LIGAMENTOUS COMPLEX

Injuries of the lateral collateral ligamentous complex (LCL) are estimated to account for
only 5 percent of all knee ligament injuries.18,23 Radiographic signs suggesting LCL
injury include lateral joint space widening and medial tibial plateau fracture.18

Decision Rules for Radiography in Acute Knee Injury

For several years, researchers have been working to design protocols that may reduce the
number of radiographs used in the evaluation of extremity injuries. A good example of a
successful protocol is the one now known as the “Ottawa ankle rules.”24–27 Protocols
have also been designed for the radiologic evaluation of knee injuries.28–30 The clinical
decision rules created in Ottawa and Pittsburgh are the best known guidelines for the
appropriate use of radiographs in acute knee injuries (Table 1).

TABLE 1 Characteristics of Patients Who Should Undergo Radiography After

Knee Trauma

View Table

OTTAWA KNEE RULES

Investigators in Ottawa conducted a retrospective chart review of all patients with acute
knee injuries who presented to an emergency department over a 10-month period.8 The
knees of 74 percent of these patients were evaluated radiographically, but only 5.2
percent were found to have fractures. All charts were evaluated for the presence of 11
clinical variables: age, gender, mechanism of injury (blunt trauma or fall versus twisting),
history of swelling, history of deformity, ability to ambulate (i.e., to walk four steps),
swelling, effusion, ligamentous instability, decreased range of motion and pain on
palpation.

Logistic regression analysis found that a fall or blunt trauma mechanism of injury had a
sensitivity of 92 percent and a specificity of 57 percent for the presence of a knee
fracture.8 The addition of inability to ambulate and age (younger than 12 years and older
than 50 years) improved the specificity. The prospective part of the study found that the
combination of all three criteria was 100 percent sensitive and 79 percent specific for
knee fracture.29

In a later study,27 attending physicians in the emergency departments of two university

hospitals assessed every adult patient with an acute knee injury for 23 standardized
clinical findings. The Ottawa knee rules were derived from this study. The presence of
one or more of these findings would have identified the 68 fractures in the study
population. Furthermore, application of the Ottawa knee rules would have led to a 28
percent relative reduction in the use of radiography in the study population.

A prospective validation of the Ottawa knee rules was published in 1996.2 Attending
emergency department physicians assessed each patient for standardized clinical
variables and determined the need for radiography based on the decision rules. The rules
were assessed for their ability to correctly identify the criterion standard, which was
fracture of the knee. The study found that the decision rules were 100 percent sensitive
for identifying knee fractures, were reliable and acceptable, and had the potential to allow
physicians to reduce the use of radiography in patients with acute knee injuries. If the
decision rules were negative, the probability of a knee fracture was zero percent.

PITTSBURGH DECISION RULES

The Pittsburgh decision rules for optimizing the use of radiography in patients with acute
knee injuries were presented in 1995.31 A prospective observational study was conducted
over a 10-month period in the emergency department of a university hospital. A
standardized closed-question data collection instrument that recorded 12 historical and 26
physical examination criteria was used in the study. A clinical algorithm for the use of
radiography that requires the presence of an inability to bear weight, an effusion or an
ecchymosis was 100 percent sensitive for the detection of knee fractures. No fractures
were found in patients who did not meet one or more of the criteria. Limiting knee
radiography to patients who met these criteria would have reduced the use of radiography
by 39 percent without missing a fracture.

COMPARISON OF DECISION RULES

The Ottawa knee rules and the Pittsburgh decision rules were compared in a prospective
study of patients evaluated in the emergency departments of three teaching hospitals.32
The Pittsburgh decision rules were 99 percent sensitive and 60 percent specific for the
diagnosis of knee fractures and could have reduced the use of radiography by 52 percent,
with one missed fracture. If the rules indicated a fracture, 24.1 percent of patients actually
had a knee fracture (positive predictive value); if the rules indicated no fracture, 99.8
percent of patients did not have a knee fracture (negative predictive value). The Ottawa
knee rules were 97 percent sensitive and 27 percent specific for knee fractures, with three
fractures missed. The authors of the comparative study concluded that the Pittsburgh
decision rules were more specific, with no loss of sensitivity.

The Authors

HOWARD B. TANDETER, M.D., is a lecturer in family medicine at Ben-Gurion

University of the Negev, Beer-Sheva, Israel. After graduating from the Faculty of
Medicine at the University of Buenos Aires, Dr. Tandeter completed a family medicine
residency in Beer-Sheva and an academic fellowship at the University of Toronto,
Ontario.

PESACH SHVARTZMAN, M.D., is an associate professor and chairman of the

Department of Family Medicine at Ben-Gurion University of the Negev. He received his
medical degree from the Medical School at the Technion, Haifa, Israel, and completed a
family medicine residency in Afula, Israel. Dr. Shvartzman was a visiting professor at
McGill University Faculty of Medicine, Montreal, Quebec.

MAX A. STEVENS, M.D., is currently in private practice at Iowa Lutheran Hospital,

Des Moines. He received his medical degree from the University of Iowa College of
Medicine in Iowa City. After a transitional-year internship at the University of South
Dakota School of Medicine, Sioux Falls, Dr. Stevens completed a residency in diagnostic
radiology at Creighton University School of Medicine and Saint Joseph Hospital, Omaha.
He also completed a fellowship in musculoskeletal radiology at the University of Iowa
Hospitals and Clinics, Iowa City.
Address correspondence to Howard B. Tandeter, M.D., Department of Family Medicine,
Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel. Reprints
are not available from the authors.

The authors thank Daniel Fick, M.D., University of Iowa College of Medicine, Iowa City,
for reviewing the manuscript and assisting in the editing process.

REFERENCES

1. Shvartzman P, Oren B, Segal Z. X-rays in extremities injury. Fam Physician. [Tel

Aviv] 1988;15:404–10.

2. Stiell IG, Greenberg GH, Wells GA, McDowell I, Cwinn AA, Smith NA, et al.
Prospective validation of a decision rule for the use of radiography in acute knee injuries.
JAMA. 1996;275:611–5.

3. Simmon RR, Koenigsknecht SJ. Emergency orthopedics: the extremities. 3d ed.

Norwalk, Conn.: Appleton & Lange, 1995.

4. Harwood-Nuss A, ed. The clinical practice of emergency medicine. Philadelphia:

Lippincott, 1991.

5. Callaham ML, ed. Current therapy in emergency medicine. Toronto: Decker, 1987.

6. McConnochie KM, Roghmann KJ, Pasternack J, Monroe DJ, Monaco LP. Prediction
rules for selective radiographic assessment of extremity injuries in children and
adolescents. 1990;86:45–57.

7. Gratton MC, Salomone JA 3d, Watson WA. Clinically significant radiograph

misinterpretations at an emergency medicine residency program. Ann Emerg Med.
1990;19:497–502.

8. Stiell IG, Wells GA, McDowell I, Greenberg GH, McKnight RD, Quinn JV, et al. Use
of radiography in acute knee injuries: need for clinical decision rules. Acad Emerg Med.
1995;2:966–73.

9. Gleadhill DN, Thomson JY, Simms P. Can more efficient use be made of x-ray
examinations in the accident and emergency department? Br Med J. [Clin Res]
1987;294:943–7.

10. Long AE. Radiographic decision-making by the emergency physician. Emerg Med
Clin North Am. 1985;3:437–46.

11. Hall FM. Overutilization of radiological examinations. Radiology. 1976;120:443–8.

12. Brand DA, Frazier WH, Kohlhepp WC, Shea KM, Hoefer AM, Ecker MD, et al. A
protocol for selecting patients with injured extremities who need x-rays. N Engl J Med.
1982;306:333–9.

13. Abrams HL. The “overutilization” of x-rays. N Engl J Med. 1979;300:1213–6.

14. Angell M. Cost containment and the physician. JAMA. 1985;254:1203–7.

15. Moloney TW, Rogers DE. Medical technology—a different view of the contentious
debate over costs. N Engl J Med. 1979;301:1413–9.

16. Weinstein SL, Buckwalter JA, eds. Turek's Orthopaedics, principles and their
application. 5th ed. Philadelphia: Lippincott, 1994.

17. Smith BW, Green GA. Acute knee injuries: Part II. Diagnosis and management. Am
Fam Physician. 1995;51:799–806.

18. Manaster BJ, Ensign MF. Imaging the ligaments of the knee. Crit Rev Diagn Imaging.
1991;32:323–66.

19. Stull MA, Nelson MC. The role of MRI in diagnostic imaging of the injured knee.
Am Fam Physician. 1990;41:489–500.

20. O'Shea KJ, Murphy KP, Heekin RD, Herzwurm PJ. The diagnostic accuracy of
history, physical examination, and radiographs in the evaluation of traumatic knee
disorders. Am J Sports Med. 1996;24:164–7.

21. Ptasznik R, Feller J, Bartlett J, Fitt G, Mitchell A, Hennessy O. The value of

sonography in the diagnosis of traumatic rupture of the anterior cruciate ligament of the
knee. AJR Am J Roentgenol. 1995;164:1461–3.

22. Stäubli HU, Jakob RP. Posterior instability of the knee near extension. A clinical and
stress radiographic analysis of acute injuries of the posterior cruciate ligament. J Bone
Joint Surg. [Br] 1990;72:225–30.

23. Newman AP. Meniscal and ligamentous injuries of the knee. Top Emerg Med.
1988;10(3):1.

24. Stiell IG, Greenberg GH, McKnight RD, Nair RC, McDowell I, Worthington JR. A
study to develop clinical decision rules for the use of radiography in acute ankle injuries.
Ann Emerg Med. 1992;21:384–90.

25. Stiell IG, McKnight RD, Greenberg GH, McDowell I, Nair RC, Wells GA, et al.
Implementation of the Ottawa ankle rules. JAMA. 1994;271:827–32.
26. Stiell I, Wells G, Laupacis A, Brison R, Verbeek R, Vandemheen K, et al. Multicentre
trial to introduce the Ottawa ankle rules for use of radiography in acute ankle injuries.
Multicentre Ankle Rule Study. BMJ. 1995;311:594–7.

27. Stiell IG, Greenberg GH, Wells GA, McKnight RD, Cwinn AA, Cacciotti T, et al.
Derivation of a decision rule for the use of radiography in acute knee injuries. Ann Emerg
Med. 1995;26:405–13.

28. Rivara FP, Parish RA, Mueller BA. Extremity injuries in children: predictive value of
clinical findings. Pediatrics. 1986;78:803–7.

29. Seaberg DC, Jackson R. Clinical decision rule for knee radiographs. Am J Emerg
Med. 1994;12:541–3.

30. Weber JE, Jackson RE, Peacock WF, Swor RA, Carley R, Larkin GL. Clinical
decision rules discriminate between fractures and nonfractures in acute isolated knee
trauma. Ann Emerg Med. 1995;26:429–33.

31. Bauer SJ, Hollander JE, Fuchs SH, Thode HC Jr. A clinical decision rule in the
evaluation of acute knee injuries. J Emerg Med. 1995;13:611–5.

32. Seaberg DC, Yealy DM, Lukens T, Auble T, Mathias S. Multicenter comparison of
two clinical decision rules for the use of radiography in acute, high-risk knee injuries.
Ann Emerg Med. 1998;32:8–13.

Coordinators of this series are Thomas J. Barloon, M.D., associate professor of radiology,
and George R. Bergus, M.D., associate professor of family practice, both at the
University of Iowa College of Medicine, Iowa City.

The editors of AFP welcome the submission of manuscripts for the Radiologic Decision-
Making series. Send submissions to Jay Siwek, M.D., following the guidelines provided
in “Information for Authors.”

A Tool for Evaluating Patients With Knee

Injury
The most widely used tests may not be the most effective.

Mark H. Ebell, MD, MS

Fam Pract Manag. 2005 Mar;12(3):67-70.

A 38-year-old patient experiences sudden, severe pain in his left knee as he pivots on that
leg to lift a couch up some stairs. He is able to ambulate initially but later develops
locking relieved by shaking his leg gently. On examination, he has a small effusion, no
erythema, nearly normal range of motion and slight joint line tenderness medially. There
is no tenderness of the patella or head of the fibula. How would you evaluate this patient?

Treatment options
Physical examination maneuvers such as the Lachman test, the anterior drawer test, the
pivot test and the McMurray test have traditionally been recommended for patients with
acute or subacute knee injury. A recent systematic review looked at which of these
maneuvers are most effective.1 The systematic review identified 35 studies involving the
maneuvers that used arthroscopic results as the reference standard. Although most of the
studies contained design flaws (e.g., the arthroscopist was not blinded to the physical
examination findings), they still provide important guidance regarding the relative
accuracy of the most widely used maneuvers.

Findings from the systematic review are summarized in "Comparing maneuvers." They
suggest that a positive Lachman test or pivot test is strong evidence in favor of an anterior
cruciate ligament (ACL) tear, while a negative Lachman test is fairly good evidence
against that injury. Although widely used, the anterior drawer is actually the least
accurate maneuver for diagnosing this injury. Regarding meniscal injury, joint line
tenderness is not very helpful at ruling in or ruling out the injury, while the McMurray
test is most helpful when positive.

Radiography is also widely used but in many cases is unhelpful. Several clinical decision
rules have been developed to assist physicians in identifying patients who are at very low
risk of bony injury and do not require radiograph. The Pittsburgh Knee Rule recommends
a radiograph for anyone with a fall or blunt-trauma mechanism, anyone younger than 12
years or older than 50 years, and anyone unable to take four weight-bearing steps in the
emergency department (or, presumably, the primary care office).2 In a prospective
validation by the developers of the rule using a convenience sample of 934 patients age 6
years to 96 years with acute knee injury, the rule was 99 percent sensitive (which
indicates a very low rate of false negatives) and 60 percent specific (which indicates a
moderate rate of false positives).3 Twenty-five percent of the patients with a positive
Pittsburgh Knee Rule evaluation had a fracture. Most importantly, 99.7 percent with a
negative evaluation using the Pittsburgh Knee Rule had no fracture.

The Ottawa Knee Rule recommends a radiograph if any of the following characteristics
are present: age 55 years or older, tenderness at the head of the fibula, isolated tenderness
of the patella (i.e., no bone tenderness of knee other than patella), inability to flex knee to
90 degrees and inability to take four weight-bearing steps (regardless of limping) both at
the time of injury and in the exam room. This rule has been more extensively validated in
a greater variety of adult populations4 than other rules and was therefore recommended
in a recent systematic review as the preferred clinical decision rule for acute knee injury.1
However, a study of the Ottawa Knee Rule that included adults and children3 and one of
children only5 both showed lower sensitivity than the Pittsburgh Knee Rule; therefore,
the Ottawa Knee Rule should not be used in pediatric populations. The Pittsburgh Knee
Rule found adequate sensitivity in a mixed population of adults and children by ordering
a radiograph for children under age 12.3

COMPARING MANEUVERS

The following table compares the accuracy of specific physical examination maneuvers
for the diagnosis of knee injuries.1

View Table

Putting it into practice

A suggested encounter form for patients presenting with acute knee injury is shown
below. It reminds physicians to use the four most accurate clinical examination
maneuvers and to follow guidelines for radiography based on the Ottawa Knee Rule. It
also reminds physicians to consider radiographs in all children under age 12, given the
results for the Pittsburgh Knee Rule. The reverse side of the form illustrates the physical
exam maneuvers.

Using the encounter form to treat the patient described earlier, the physician would see
that radiography is not indicated. The Lachman test or pivot test would be most effective
for diagnosing ACL tear, while the McMurray test would be most effective for
diagnosing meniscal tear. In fact, a positive McMurray test proved itself reliable for this
patient in real life. Although an MRI was negative, a tear of the medial meniscus was
discovered during arthroscopic exploration. (Editor’s note: this was the author’s
experience with his own knee injury.)

ACUTE KNEE INJURY ENCOUNTER FORM

Common Maneuvers of the Knee for Assessing Possible Ligamentous and Meniscal
Damage

Anterior drawer test(Top left). Place patient supine, flex the hip to 45 degrees and the
knee to 90 degrees. Sit on the dorsum of the foot, wrap your hands around the hamstrings
(ensuring that these muscles are relaxed), then pull and push the proximal part of the leg,
testing the movement of the tibia on the femur. Do these maneuvers in three positions of
tibial rotation: neutral, 30 degrees externally rotated, and 30 degrees internally rotated. A
normal test result is no more than 6 to 8 mm of laxity.

Lachman test (Top right). Place patient supine on examining table, leg at the examiner’s
side, slightly externally rotated and flexed (20 to 30 degrees). Stabilize the femur with
one hand and apply pressure to the back of the knee with the other hand with the thumb
of the hand exerting pressure placed on the joint line. A positive test result is movement
of the knee with a soft or mushy end point.

Pivot test (Bottom left). Fully extend the knee, rotate the foot internally. Apply a valgus
stress while progressively flexing the knee, watching and feeling for translation of the
tibia on the femur.

McMurray test (Bottom right). Flex the hip and knee maximally. Apply a valgus
(abduction) force to the knee while externally rotating the foot and passively extending
the knee. An audible or palpable snap during extension suggests a tear of the medial
meniscus. For the lateral meniscus, apply a varus (adduction) stress during internal
rotation of the foot and passive extension of the knee.

Adapted with permission from Jackson JL, O’Malley PG, Kroenke K. Evaluation of
acute knee pain in primary care. Ann Intern Med. 2003;139:580.

View Large

POINT-OF-CARE SERIES

This article is part of a series that offers evidence-based tools to assist family physicians
in improving their decision making at the point of care. The series is produced in
partnership with American Family Physician. A related article, which also includes the
acute knee injury encounter form, appears in the March 15, 2005, issue of AFP, page
1169–1172.

Past topics in this series include sore throat, pulmonary embolism, hypertension, acute
otitis media and angioplasty risk. All tools are available free online at
http://www.aafp.org/fpm/toolbox.

Dr. Ebell is deputy editor for evidence-based medicine for American Family Physician.
He is an associate professor in the Department of Family Practice at Michigan State
University College of Human Medicine, East Lansing, and is in private practice in
Athens, Ga. Conflicts of interest: none reported.

Send comments to fpmedit@aafp.org.

1. Jackson JL, O’Malley PG, Kroenke K. Evaluation of acute knee pain in primary care.
Ann Intern Med. 2003;139:575–588.

2. Seaberg DC, Jackson R. Clinical decision rule for knee radiographs. Am J Emerg Med.
1994;12:541–543.

3. Seaberg DC, Yealy DM, Lukens T, Auble T, Mathias S. Multicenter comparison of two
clinical decision rules for the use of radiography in acute, high-risk knee injuries. Ann
Emerg Med. 1998;32:8–13.

4. Bachmann LM, Haberzeth S, Steurer J, ter Riet G. The accuracy of the Ottawa Knee
Rule to rule out knee fractures: a systematic review. Ann Intern Med. 2004;140:121–124.

5. Khine H, Dorfman DH, Avner JR. Applicability of Ottawa knee rule for knee injury in
children. Pediatr Emerg Care. 2001;17:401–404.
Guide to Dietary Supplements Most
Commonly Used in Pain Management
Dietary supplements can be a useful part of an integrative approach to the treatment of
pain.
By David Kiefer, MD and Traci Pantuso, MS
Page 1 of 3

13

Patients with chronic pain who seek medical advice about choosing a vitamin or
supplement need to be educated about the risks/benefits of these agents. This article
reviews the evidence for the most common supplements used to treat pain, recognizing
the importance of an appropriate work-up, including a comprehensive history, physical
examination, and relevant diagnostic studies to establish a correct diagnosis and treatment
plan. Although in some cases there is overlap, pain supplements can be divided into those
used to treat fibromyalgia, headache, or joint pain—osteoarthritis (OA) or rheumatoid
arthritis (RA) (Tables 1 and 2). Treatments for other pain entities, such as low back pain,
pain from acute injuries, and cancer-related pain are beyond the scope of this article.

Fibromyalgia

Reviews of dietary supplements for the treatment of fibromyalgia have found some
supplements to be of benefit for specific indications, such as anthocyanidins for sleep
disturbances and topical capsaicin (0.025%) for joint tenderness but not for overall
pain.1,2 However, the results of clinical trials of soy, malic acid, and some Chinese
medicines have either been inconclusive or negative.1-3 For the treatment of fibromyalgia,
some of the best evidence supports the use of S-adenosylmethionine (SAMe), a
compound that exists naturally as a result of mammalian metabolism but is used in
supraphysiologic doses for some medical conditions.4 A review of seven clinical trials
found that SAMe benefits fibromyalgia-related depression and tender point pain severity.4

The amino acid 5-hydroxytryptophan (5-HTP) crosses the blood–brain barrier and may
have effects on serotonin levels. The agent was researched in two small clinical trials
more than 20 years ago.5 In the first trial, an open- label, 3-month study using 100 mg of
5-HTP three times daily in 50 people, researchers reported improvements in number of
tender points, anxiety, sleep, and pain scores compared with baseline (P<0.001).6 The
second trial, a double-blind, placebo-controlled trial, documented similar improvements
in symptoms after 1 month of 5-HTP at a dosage of 100 mg three times daily.7 Concerns
about eosinophilia myalgia syndrome due to a suspect batch of 5-HTP more than 20 years
ago still compels clinicians to use reputable 5-HTP manufacturers.

Headache
Most research on dietary supplements has explored the use of supplements to prevent or
treat migraine headaches.9 One agent, vitamin B2 (riboflavin) practically has become
standard of care in the prevention of migraines. One study demonstrated that 400 mg per
day of riboflavin significantly decreased migraine frequency (P=0.005) and the number
of days with headache (P=0.012) in 55 people after 3 months of treatment.10

Another supplement that is commonly used to prevent migraines is feverfew (Tanacetum

parthenium), although reviews have shown conflicting results about its efficacy.11,12
Variability in the type of feverfew tested—from powdered herb in capsules to alcohol
extracts—can lead to a range in concentrations of parthenolide, the active component.13
One research group found that a feverfew C02 extract (MIG-99), at a dosage of 6.25 mg
three times daily, decreased migraine frequency over 16 weeks.14 From the baseline of
4.76 attacks per month, migraine frequency decreased by 1.9 attacks in the MIG-99 group
and by 1.3 attacks in the placebo group (P=0.0456).

A rhizome extract of the butterbur plant (Petasites hybridus) also has shown efficacy for
migraine prevention, likely due to smooth muscle relaxation and leukotriene inhibition.15
Clinical trials have shown that 50 to 75 mg twice daily of a standardized butterbur extract
(Petadolex, Weber & Weber) decreased the number of migraine attacks per month and led
to fewer patients needing migraine medication treatments.16,17 A standardized extract (eg,
Petadolex) free of the hepatotoxic pyrrolizidine alkaloids must be used.

Coenzyme Q10 (CoQ10), with a dosage range of 150 to 300 mg per day, and magnesium,
300 to 600 mg per day also have been studied for migraine prevention.13,18,19 These two
nutritents have been found to decrease migraine frequency and severity, the number of
headache days, and, in the case of CoQ10, days with nausea. In addition, both CoQ10 and
magnesium are considerations for pediatric migraines, whereas magnesium is also used
for migraine headaches associated with mentruation.

Joint Pain

As demonstrated by in vitro research, many dietary supplements affect the production or

activity of pro-inflammatory mediators, in some cases via cyclooxygenase-1 or -2 (COX-
1, COX-2) or lipoxygenase (LOX) inhibition. For example, turmeric (Curcuma longa),
with the active ingredient curcumin, has been shown to inhibit numerous inflammatory
mediators, such as nuclear factor-kappa B (NF-κB), prostaglandin-E2, leukotrienes, and
nitric oxide.20 References are made in review articles to preliminary clinical trials (one
used 1,200 mg of curcumin daily in patients with RA), but more definitive research is
needed to establish dosages and efficacy.21

Boswellia (Boswellia serrata) often is combined with turmeric. In one crossover trial in
30 patients with knee OA, the boswelia group (333 mg three times daily) had less
swelling, pain, and loss of joint movement compared with the control group (P<0.001),
although no radiologic changes in the knee joint were observed.22 Another boswellia
extract (5-Loxin, PL Thomas) was studied in 75 patients with knee OA. Patients were
randomly assigned to receive either 100 or 250 mg of 5-Loxin or a placebo daily for 90
days. At the end of the study, both doses of 5-Loxin conferred clinically and statistically
significant improvements in pain scores and physical function scores in OA patients
(P<0.001-0.002), noted the investigators. Significant improvements in pain score and
functional ability were recorded in the treatment group supplemented with 250 mg 5-
Loxin as early as 7 days after the start of treatment.23

Ginger (Zingiber officinale) rhizome contains compounds such as shogaols that inhibit
pro-inflammatory prostaglandins. Preliminary clinical trials have reported improvement
in knee pain. In a placebo-controlled study, ginger combined with galanga (Alpinia
galanga) was given to 261 people with knee OA. The researchers reported less knee pain
in the treatment group compared with the control group (63% vs 50%; P=0.048).24 In
another study, ginger extract was found to be less effective than 400 mg of ibuprofen
three times daily in improving pain scores in patients with knee or hip OA.25 Overall,
there are conflicting results about ginger’s effectiveness in the literature.26,27

View Sources

Glucosamine and chondroitin, primarily used for knee OA, have been studied in
numerous clinical trials and systematic reviews; the positive effects of glucosamine on
symptoms and joint space narrowing in OA found in reviews seem to be tempered by the
inclusion of higher-quality studies. The recent 2-year GAIT (Glucosamine/chondroitin
Arthritis Intervention Trial) found insignificant trends for improvement in joint pain with
celecoxib (Celebrex) 200 mg per day and glucosamine hydrochloride (500 mg three times
daily); there was no effect with chondroitin sulfate (400 mg three times daily), or with the
glucosamine-chondroitin combination.28 It is possible that glucosamine sulfate may be
more effective than the hydrochloride form, but that is still being debated, as are the exact
mechanisms of action.29,30 The ongoing LEGS (Long Term Evaluation of Glucosamine
Sulphate) study is assessing the efficacy of this formulation.

Methylsulfoylmethane (MSM) has been studied in OA, in both oral and topical
formulations, often in combination with other nutraceuticals.31 A few clinical trials have
been conducted, including a placebo-controlled pilot study of 50 people with knee pain.
Compared with placebo, MSM (3 g twice daily) produced significantly less pain and
impairment after 3 months (P<0.05).32 High-quality trials, especially with parallel
pharmaceutical treatment groups, are needed.

Devil’s claw (Harpagophytum procumbens) is an African plant that has been used
traditionally for arthritis, low back pain, and headache.33 The anti-inflammatory activities
of Devil’s claw are thought to be due to an iridoid glycoside, harpagoside, possibly
through its inhibition of various inflammatory mediators via NF-κB and COX-2
inhibition.33 Systematic reviews have found that harpagoside dosages of 50 to 100 mg per
day may be effective in decreasing spine, knee, and hip pain.2,27

Avocado-soybean unsaponifiables (ASU) are derived from the unsaponifiable fraction of

avocado and soybean oil and contain phytosterols, β-sterols, stigasterol, and campestrol.
Four clinical trials of ASU found positive effects for knee or hip OA over 3 to 6 months
(less pain and swelling); although joint space width did not change overall, a subgroup
analysis may have found a reduction in progressive joint space loss in people with
advanced joint space narrowing.22,34 All four trials used 300 to 600 mg daily of the
Piascledine 300 formulation of ASU.

Salix alba, or white willow, one of the plants from which aspirin (acetylsalicylic acid,
ASA) and related compounds were discovered and derived, contains glycosides (salicin,
salicortin, fragilin, and tremulacin) and the primary metabolite, salicylic acid, that act as
nonselective COX-1/COX-2 inhibitors.35,36 Two reviews detailed the use of Salix alba
(120-240 mg per day of salicin) for back pain,37,38 while a third review looked at herbal
preparations for OA, finding positive effects for one herbal product containing 100 mg of
powdered Salix alba bark and four other plants.39 A multifaceted trial in 127 people with
knee or hip OA randomized to 240 mg of salicin daily (from S. daphnoides bark),
diclofenac 100 mg daily, or placebo, and 26 people with RA randomized to either 240 mg
of salicin daily or placebo, found no reduction in pain with salicin for either OA or RA
after 6 weeks.40 In the OA arm, pain scores decreased by 8 mm (17%) in the willow bark
group and by 23 mm (47%) in the diclofenac group compared with 5 mm (10%) in the
placebo group. In the RA arm, the mean reduction of pain on the visual analog scale
(VAS) was 8 mm (15%) in the willow bark group compared with 2 mm (4%) in the
placebo group. The difference was not statistically significant, noted the investigators. It
is possible that Salix alba is more effective than Salix daphnoides. Estimates are that 240
mg of salicin is equivalent to 50 mg of ASA,41 leading most experts to consider Salix
alba as an adjunctive therapy for pain, at best.

The two species of cat’s claw, or uña de gato (Uncaria tomentosa and U. guianensis),
contain a variety of compounds, including pentacyclic oxindole alkaloids, that have
antioxidant and anti-inflammatory effects via suppression of TNF-α and NF-κB.42 In a
double-blind trial, 40 patients with RA were randomized to receive either a 20 mg
capsule of U. tomentosa root extract (Krallendorn) or placebo three times daily for 6
months.43 Patients taking cat’s claw had a greater reduction in painful joints than the
control group (53.2% vs 24.1%, respectively; P=0.044), but there were no differences in
the number of swollen joints, the duration of morning stiffness, or laboratory parameters.
Another trial randomized 45 people with knee OA to 100 mg per day of a freeze-dried
preparation of U. guianensis bark (30 patients) or placebo (15 patients) for 4 weeks.44 The
cat’s claw group had significantly less knee pain with activity, even after just 1 week of
treatment.

Baikal, or Chinese, skullcap (Scuttelaria baicalensis/barbata), has traditional use as an

anti-inflammatory. Recently, an extract of the root has been combined with the bark of
Acacia catechu in a blend called flavocoxid (Limbrel, Primus Pharmaceuticals)
containing from the two plants respectively, baicalin and catechin—flavonoids with anti-
oxidant and anti-inflammatory activity. In one double-blind clinical trial, 103 people with
knee OA were given either 500 mg twice daily of flavocoxid or naproxen; both groups
improved equally from baseline (P<0.01), but without a control group, it is difficult to
determine how much of that improvement is due to placebo effect.45

SAMe also has been studied in people with OA and was the subject of an 11-study meta-
analysis.46 Two of the 11 studies allowed the researchers to conclude that SAMe versus
placebo improves functional limitations (effect size 0.31; 95% confidence interval, 0.098-
0.519) but not pain. However, when compared with nonsteroidal anti-inflammatory drugs
(NSAIDs), SAMe was as effective as NSAIDs in addressing both pain and functional
limitations, and had less side effects than NSAIDs. There was a significant amount of
heterogeneity in the included studies (ie, dosing, length, etc.), prompting the researchers
to recommended further clinical trials.

Omega-3 fatty acids, especially the marine-derived eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA) are thought to lessen inflammation by competing with
arachidonic acid as substrates for metabolism by COX and LOX.47 Most of the clinical
trials have focused on fish oil (at least 2.7 g EPA plus DHA daily, results may not be
apparent for 3 to 4 months) in RA, although there also has been research on flax seeds or
flax seed oil; benefits have been noted in patient-assessed pain, morning stiffness,
number of affected joints, and NSAID use.48,49
Conclusion
There are many dietary supplements, with varying degrees of supporting scientific
evidence, for pain conditions such as fibromyalgia, headache, and joint pain. In some
cases, after addressing any relevant nutraceutical-pharmaceutical interactions, such
products can be a useful part of an integrative approach to the treatment of pain, while the
medical community awaits further research to refine and improve the use of these
vitamins, herbs, and other compounds.

 View Sources1. De Silva V, El-Metwally A, Ernst E, et al. Evidence for the

efficacy of complementary and alternative medicine in the management of
fibromyalgia: a systematic review. Rheumatology (Oxford). 2010;49(6):1063-
1068.
 2. Ernst E. Herbal medicine in the treatment of rheumatic diseases. Rheum Dis
Clin North Am. 2011;37(1):95-102.
 3. Russell IJ, Michalek JE, Flechas JD, Abraham GE. Treatment of fibromyalgia
syndrome with Super Malic: a randomized, double blind, placebo controlled,
crossover pilot study. J Rheumatol. 1995;22(5):953-958.
 4. Fetrow CW, Avila JR. Efficacy of the dietary supplement S-adenosyl-l-
methionine. Ann Pharmacother. 2001;35(11):1414-1425.
 5. Turner EH, Loftis JM, Blackwell AD. Serotonin a la carte: supplementation
with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther.
2006;109(3):325-338.
 6. Sarzi Puttini P, Caruso I. Primary fibromyalgia syndrome and 5-hydroxy-l-
tryptophan: a 90-day open study. J Int Med Res. 1992;20(2):182-189.
 7. Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V. Double-blind study of 5-
hydroxytryptophan versus placebo in the treatment of primary fibromyalgia
syndrome. J Int Med Res. 1990;18(3):201-209.
 8. Das YT, Bagchi M, Bagchi D, Preuss HG. Safety of 5-hydroxy-l-tryptophan.
Toxicol Lett. 2004;150(1):111-122.
 9. Nicholson RA, Buse DC, Andrasik F, Lipton RB. Nonpharmacologic
treatments for migraine and tension-type headache: how to choose and when to
use. Curr Treat Options Neurol. 2011;13(1):28-40.
 10. Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in
migraine prophylaxis. Neurology. 1998;50(2):466-470.
 11. Vogler BK, Pittler MH, Ernst E. Feverfew as a preventive treatment for
migraine: a systematic review. Cephalalgia. 1998;18(10):704-708.
 12. Pittler MH, Ernst E. Feverfew for preventing migraine. Cochrane Database
 Syst Rev. 2004;(1):CD002286.
 13. Schiapparelli P, Allais G, Castagnoli Gabellari I, Rolando S, Terzi MG,
Benedetto C. Non-pharmacological approach to migraine prophylaxis: part II.
Neurol Sci. 2010;31 Suppl 1:S137-S139.
 14. Diener HC, Pfaffenrath V, Schnitker J, Friede M, Henneicke-von Zepelin HH.
Efficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine
prevention—a randomized, double-blind, multicentre, placebo-controlled study.
Cephalalgia. 2005;25(11):1031-1041.
 15. Sutherland A, Sweet BV. Butterbur: an alternative therapy for migraine
prevention. Am J Health Syst Pharm. 2010;67(9):705-711.
 16. Diener HC, Rahlfs VW, Danesch U. The first placebo-controlled trial of a
special butterbur root extract for the prevention of migraine: reanalysis of efficacy
criteria. Eur Neurol. 2004;51(2):89-97.
 17. Lipton RB, Göbel H, Einhäupl KM, Wilks K, Mauskop A. Petasites hybridus
root (butterbur) is an effective preventive treatment for migraine. Neurology.
2004;63(12):2240-2244.
 18. Taylor FR. Nutraceuticals and headache: the biological basis. Headache.
2011;51(3):484-501.
 19. Sun-Edelstein C, Mauskop A. Alternative headache treatments: nutraceuticals,
behavioral and physical treatments. Headache. 2011;51(3):469-483.
 20. Henrotin Y, Clutterbuck AL, Allaway D, et al. Biological actions of curcumin
on articular chondrocytes. Osteoarthritis Cartilage. 2010;18(2):141-149.
 21. Efthimiou P, Kukar M. Complementary and alternative medicine use in
rheumatoid arthritis: proposed mechanism of action and efficacy of commonly
used modalities. Rheumatol Int. 2010;30(5):571-586.
 22. Cameron M, Gagnier JL, Little CV, Parsons TJ, Blümle A, Chrubasik S.
Evidence of effectiveness of herbal medicinal products in the treatment of
arthritis. Part 1: osteoarthritis. Phytother. Res. 2009;23(11):1497-1515.
 23. Sengupta K, Alluri KV, Satish AR, et al. A double blind, randomized, placebo
controlled study of the efficacy and safety of 5-Loxin for treatment of
osteoarthritis of the knee. Arthritis Res Ther. 2008;10(4):R85.
 24. Altman RD, Marcussen KC. Effects of a ginger extract on knee pain in
patients with osteoarthritis. Arthritis Rheum. 2001;44(11):2531-2538.
 25. Bliddal H, Rosetzsky A, Schlichting P, et al. A randomized, placebo-
controlled, cross-over study of ginger extracts and ibuprofen in osteoarthritis. J
Osteoarthritis Cartilage. 2000;8(1):9-12.
 26. White B. Ginger: an overview. Am Fam Physician. 2007;75(11):1689-1691.
 27. Chrubasik JE, Roufogalis BD, Chrubasik S. Evidence of effectiveness of
herbal antiinflammatory drugs in the treatment of painful osteoarthritis and
chronic low back pain. Phytother Res. 2007;21(7):675-683.
 28. Sawitzke AD, Shi H, Finco MF, et al. Clinical efficacy and safety of
glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken
to treat osteoarthritis of the knee: 2-year results from GAIT. Ann Rheum Dis.
2010;69(8):1459-1464.
 29. Dahmer S, Schiller RM. Glucosamine. Am Fam Physician. 2008;78(4):471-
476.
 30. Miller KL, Clegg DO. Glucosamine and chondroitin sulfate. Rheum Dis Clin
North Am. 2011;37(1):103-118.
 31. Brien S, Prescott P, Bashir N, Lewith H, Lewith G. Systematic review of the
nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane
(MSM) in the treatment of osteoarthritis. Osteoarthritis Cartilage.
2008;16(11):1277-1288.
 32. Kim LS, Axelrod LJ, Howard P, Buratovich N, Waters RF. Efficacy of
methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical
trial. Osteoarthritis Cartilage. 2006;14(3):286-294.
 33. Setty AR, Sigal LH. Herbal medications commonly used in the practice of
rheumatology: mechanisms of action, efficacy, and side effects. Semin Arthritis
Rheum. 2005;34(6):773-784.
 34. Christensen R, Bartels EM, Astrup A, Bliddal H. Symptomatic efficacy of
avocado-soybean unsaponifiables (ASU) in osteoarthritis (OA) patients: a meta-
analysis of randomized controlled trials. Osteoarthritis Cartilage. 2008;16(4):399-
408.
 35. Tyler VE. Herbs of Choice. New York: Pharmaceutical Products Press; 1994.
 36. Fuster V, Sweeny JM. Aspirin: a historical and contemporary therapeutic
overview. Circulation. 2011;123(7):768-778.
 37. Ernst E, Chrubasik S. Phyto-anti-inflammatories. A systematic review of
randomised, placebo-controlled, double-blind trials. Rheumatic Dis Clin North
Am. 2000;26(1):13-27.
 38. Gagnier JJ, van Tulder MW, Berman BM, Bombardier C. Herbal medicine for
low back pain. Cochrane Database Syst Rev. 2006;(2):CD004504.
 39. Little CV, Parsons T. Herbal therapy for treating osteoarthritis. Cochrane
Database Syst Rev. 2001;(1):CD002947.
 40. Biegert C, Wagner I, Lüdtke R, et al. Efficacy and safety of willow bark
extract in the treatment of osteoarthritis and rheumatoid arthritis: results of 2
randomized double-blind controlled trials. J Rheumatol. 2004;31(11):2121-2130.
 41. Chrubasik S, Eisenberg E, Balan E, Weinberger T, Luzzati R, Conradt C.
Treatment of low back pain exacerbations with willow bark extract: a randomized
double-blind study. Am J Med. 2000;109(1):9-14.
 42. Erowele GI, Kalejaiye AO. Pharmacology and therapeutic uses of cat’s claw.
Am J Health Syst Pharm. 2009;66(11):992-995.
 43. Mur E, Hartig F, Eibl G, Schirmer M. Randomized double blind trial of an
extract from the pentacyclic alkaloid-chemotype of Uncaria tomentosa for the
treatment of rheumatoid arthritis. J Rheumatol 2002;29(4):678-681.
 44. Piscoya J, Rodriguez Z, Bustamante SA, Okuhama NN, Millar MJ, Sandoval
M. Efficacy and safety of freeze-dried cat’s claw in osteoarthritis of the knee:
mechanisms of action of the species Uncaria guianensis. Inflamm Res
2001;50(9):442-448.
 45. Levy RM, Saikovsky R, Shmidt E, Khokhlov A, Burnett BP. Flavocoxid is as
effective as naproxen for managing the signs and symptoms of osteoarthritis of
the knee in humans: a short-term randomized, double-blind pilot study. Nutr Res.
2009;29(5):298-304.
 46. Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BM. Safety and efficacy
of S-adenosylmthionine (SAMe) for osteoarthritis. J Fam Pract. 2002;51(5):425-
430.
 47. Cleland LG, James MJ, Proudman SM. The role of fish oils in the treatment of
rheumatoid arthritis. Drugs. 2003;63(9):845-853.
 48. Covington MB. Omega-3 fatty acids. Am Fam Physician. 2004;70(1):133-
140.
 49. Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3
polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain.
2007;129(1-2):210-223.
Knee Surgery, Sports Traumatology, Arthroscopy
September 2011, Volume 19, Issue 9, pp 1442-1452

The painful knee after TKA: a diagnostic

algorithm for failure analysis
 S. Hofmann,
 G. Seitlinger,
 O. Djahani,
 M. Pietsch

Abstract
Pain after total knee arthroplasty (TKA) represents a common observation in about 20%
of the patients after surgery. Some of these painful knees require early revision surgery
within 5 years. Obvious causes of failure might be identified with clinical examinations
and standard radiographs only, whereas the unexplained painful TKA still remains a
challenge for the surgeon. It is generally accepted that a clear understanding of the failure
mechanism in each case is required prior considering revision surgery. A practical 10-step
diagnostic algorithm is described for failure analysis in more detail. The evaluation of a
painful TKA includes an extended history, analysis of the type of pain, psychological
exploration, thorough clinical examination including spine, hip and ankle, laboratory
tests, joint aspiration and test infiltration, radiographic analysis and special imaging
techniques. It is also important to enquire about the length and type of conservative
therapy. Using this diagnostic algorithm, a sufficient failure analysis is possible in almost
all patients with painful TKA.

Level of evidence IV.

Look
Inside
8 Citations
Rheum Dis Clin North Am. Author manuscript; available in PMC Aug 1, 2009.
Published in final edited form as:
Rheum Dis Clin North Am. Aug 2008; 34(3): 623–643.
doi: 10.1016/j.rdc.2008.05.004
PMCID: PMC2597216
NIHMSID: NIHMS67188

The symptoms of OA and the genesis of

pain
David J. Hunter, MBBS PhD,1,2 Jason J. McDougall, BSc PhD,3 and Francis J. Keefe4
Author information ► Copyright and License information ►
The publisher's final edited version of this article is available at Rheum Dis Clin North
Am
See other articles in PMC that cite the published article.
Go to:

Introduction
Symptomatic osteoarthritis (OA) causes substantial physical and psychosocial disability
(1). In the early 1990’s, over 7 million Americans were limited in their ability to
participate in their main daily activities, such as going to school or work or maintaining
their independence — simply because of their arthritis (2). Interestingly, the risk for
disability (defined as needing help walking or climbing stairs) attributable to knee OA is
as great as that attributable to cardiovascular disease and greater than that due to any
other medical condition in elderly persons (1). Like arthritis prevalence, the prevalence of
arthritis-related disability is also expected to rise by the year 2020, when an estimated
11.6 million people will be affected (2).

Compounding this picture are the enormous financial costs that our nation bears for
treating arthritis, its complications, and the disability that results from uncontrolled
disease. The total annual cost in the United States is almost $65 billion— a figure
equivalent to a moderate national recession (3). This amount includes an estimated
medical bill of $15 billion each year for such expenses as 39 million physician visits and
more than half a million hospitalizations (CDC, unpublished data). OA accounts for 90%
of hip and knee replacements (4). The balance is largely due to indirect costs such as
those from wage losses (3). Thus, arthritis has become one of our most pressing public
health problems —a problem that is expected to worsen in the next millennium with the
increasing prevalence of this disease.

This review delineates the characteristic symptoms and signs associated with OA and
how they can be used to make the clinical diagnosis. The predominant symptom in most
patients is pain. The remainder of the review focuses on what we know causes pain in OA
and contributes to its severity. Much has been learnt over recent years however for the
budding researcher much of this puzzle remains unexplored or inadequately understood.

Go to:

What is OA?
OA can be viewed as the clinical and pathological outcome of a range of disorders that
results in structural and functional failure of synovial joints (5). OA occurs when the
dynamic equilibrium between the breakdown and repair of joint tissues is overwhelmed
(6). This progressive joint failure may cause pain, physical disability, and psychological
distress (1), although many persons with structural changes consistent with OA are
asymptomatic (7). The reasons why there is this disconnect between disease severity and
the level of reported pain and disability is unknown.

Typically OA presents as joint pain. During a one year period, 25% of people over 55
years have a persistent episode of knee pain, of whom about one in six consult their
general practitioner about it (8). Approximately 50% of these persons have radiographic
knee OA. The usefulness of x-rays relates more importantly to the exclusion of other
diagnostic possibilities rather than confirmation of osteoarthritic disease (9). Factors
differentiating symptomatic OA from asymptomatic radiographic disease are largely
unknown. Symptomatic knee OA (pain on most days and radiographic features consistent
with OA) occurs in approximately 12% of those aged over 55 (8).

While OA is common in the knee, it is even more prevalent in the hands, especially the
distal (DIP) and proximal (PIP) interphalangeal joints and the base of the thumb (CMC).
When symptomatic, especially so for the base of thumb joint, hand OA is associated with
functional impairment (10;11). OA of the thumb carpo-metacarpal joint is a common
condition that can lead to substantial pain, instability, deformity, and loss of motion (12).
Over the age of 70 years, approximately 5% of women and 3% of men have symptomatic
OA affecting this joint with impairment of hand function (10).

The prevalence of hip OA is about 9% in Caucasian populations (13). In contrast, studies

in Asian, black, and East Indian populations indicate a very low prevalence of hip OA
(14). The prevalence of symptomatic hip OA is approximately 4% (15).

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What are the characteristic symptoms of OA?

The joint pain of OA is typically described as exacerbated by activity and relieved by
rest. More advanced OA can cause rest and night pain leading to loss of sleep which
further exacerbates pain. The cardinal symptoms that suggest a diagnosis of OA include:
  pain (typically described as activity related or mechanical, may occur with rest in
advanced disease; often deep, aching and not well localized; usually of insidious
onset;),
 reduced function
 stiffness (of short duration, also termed “gelling” i.e. short-lived stiffness after
inactivity),
 joint instability, buckling or giving way
 patients may also complain of reduced movement, deformity, swelling, crepitus,
and increased age (OA is unusual before age 40) in the absence of systemic
features (such as fever),
 and when pain persists pain-relate psychological distress.

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Tailoring the physical exam-what signs are associated

with OA
Physical examination should include an assessment of body weight and body mass index,
joint range of motion, the location of tenderness, muscle strength, and ligament stability.
For lower limb joint involvement, this should include assessment of body mass and
postural alignment in both standing and walking (16). A goniometer can be used to permit
the examiner to visually bisect the thigh and lower leg along their lengths. The centers of
both the patella and ankle should be located and marked with a pen. The center of the
goniometer is placed on the center of the patella, and the arms of this goniometer are
extended along the center of the thigh and along the axis of the lower leg to the center of
the ankle.

The features on physical examination that suggest a diagnosis of OA include:

 Tenderness, usually located over the joint line

 Crepitus with movement of the joint
 Bony enlargement of the joint, e.g., Heberden's and Bouchard's nodes, squaring of
the first CMC, typically along the affected joint line in the knee.
 Restricted joint range of motion
 Pain on passive range of motion
 Deformity, e.g., angulation of the DIP and PIP joints, varus (bowed legs)
deformity of the knees
 Instability of the joint
 Altered gait
 Muscle atrophy or weakness
 Joint effusion

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The Diagnosis of OA
Bearing in mind that radiographs are notoriously insensitive to the earliest pathological
features of OA, the absence of positive radiographic findings should not be interpreted as
confirming the complete absence of symptomatic disease. Conversely, the presence of
positive radiographic findings does not guarantee that an osteoarthritic joint is also the
active source of the patient’s current knee or hip symptoms where other sources of pain
including periarticular sources such as pes anserine bursitis at the knee and trochanteric
bursitis at the hip often contribute (7). According to the ACR criteria for classification of
hand OA (unlike the hip and knee where radiographs enhance the sensitivity and
specificity), x-rays are less sensitive and specific than physical examination in the
diagnosis of symptomatic hand OA (17).

In clinical practice the diagnosis of OA should be made on the basis of your history
and physical examination and the role of radiography is to confirm this clinical
suspicion and rule out other conditions.

When disease is advanced, it is visible on plain radiographs, which show narrowing of

joint space, osteophytes, and sometimes changes in the subchondral bone. MRI can be
used in infrequent circumstances to facilitate the diagnosis of other causes of joint pain
that can be confused with OA (osteochondritis dissecans, avascular necrosis). An
unfortunate consequence of the frequent use of MRI in clinical practice is the frequent
detection of meniscal tears. In the interests of preserving menisci an important cautionary
note; meniscal tears are nearly universal in persons with knee OA and are not necessarily
a cause of increased symptoms (18). The penchant to remove menisci is to be avoided,
unless there are symptoms of locking or extension blockade (19).

Do not rely upon laboratory testing to establish the diagnosis of OA. Because OA is a
non-inflammatory arthritis, laboratory findings are expected to be normal.

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What are the diagnostic criteria for osteoarthritis?

When making the diagnosis of OA, consider using the criteria of the American College of
Rheumatology for diagnostic purposes and classification of OA of the hip, knee, and
hands in patients with pain in these joints (17;20). These are the criteria that are used in
research studies and should be used to inform your diagnosis in individuals but not
limiting your information gathering to these criteria and considering the wealth of other
information that patients with OA may provide that can help to either confirm or refute an
OA diagnosis.

In clinical practice the diagnosis of OA should be made on the basis of your history and
physical examination and the role of radiography is to confirm this clinical suspicion and
rule out other conditions.

In the process of taking a history it is important to ask how the pain has affected the
persons function at home, work and in recreational activities. Also, ask about how the
person is coping with pain and how well that is going. It is important to look for signs of
psychological distress, e.g. signs of anxiety such as excessive pain avoidant posturing,
sleep onset insomnia, or signs of depression such as early morning wakening, weight
loss, irritability, or a marked in increase in memory/concentration problems.

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Factors that contribute to pain

The source of pain is not particularly well understood and is best framed in a
biopsychosocial framework (posits that biological, psychological and social factors all
play a significant role in pain in OA) (21). Figure 1 depicts a schematic representing
some of this complexity.

Figure 1
Future Targets to Control Osteoarthritis Pain

From a biological perspective, neuronal activity in the pain pathway is responsible for the
generation and ultimate exacerbation of the feeling of joint pain. During inflammation
chemical mediators are released into the joint which sensitize primary afferent nerves
such that normally innocuous joint movements (such as increased physical activity, high
heeled shoes, weather changes) now elicit a painful response. This is the
neurophysiological basis of allodynia i.e. the sensation of pain in response to a normally
non-painful stimulus such as walking. Over time this increased neuronal activity from the
periphery can cause plasticity changes in the central nervous system by a process termed
"wind-up". In this instance, second order neurones in the spinal cord increase their firing
rate such that the transmission of pain information to the somatosensory cortex is
enhanced. This central sensitization phenomenon intensifies pain sensation and can even
lead to pain responses from regions of the body remote from the inflamed joint i.e.
referred pain.

Constitutional factors that can predispose to symptoms include self-efficacy, pain

catastrophizing, and the social context of arthritis (social support, pain communication)
are all important considerations in understanding the pain experience.

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Local tissue pathology

The structural determinants of pain and mechanical dysfunction in OA are also not well
understood, but are believed to involve multiple interactive pathways. Articular cartilage
is both aneural and avascular. As such, cartilage is incapable of directly generating pain,
inflammation, stiffness, or any of the symptoms that patients with OA typically describe
(22). Given its relative unimportance to OA’s symptomatic presentation, it is ironic that
articular cartilage has received so much attention while other common symptom sources
in the joint are ignored.

In contrast the subchondral bone, periosteum, periarticular ligaments, periarticular muscle

spasm, synovium and joint capsule are all richly innervated and are the source of
nociception in OA.

In population studies there is a significant discordance between radiographically

diagnosed OA and knee pain (7). Whilst radiographic evidence of joint damage
predisposes to joint pain, it is clear that the severity of the joint damage on the radiograph
bears little relation to the severity of the pain experienced.

However, utilising other imaging modalities such as magnetic resonance imaging (MRI)
significant structural associations such as bone marrow lesions (23;24), sub-articular
bone attrition (25), synovitis and effusion (26;27) have been related to knee pain. It
remains unclear which of these local tissue factors predominate as until recently these
analyses did not account for the fact that much of the structural change is collinear (a
person who has more severe disease will have worse structural change in multiple tissues
including the bone synovium, etc) and were not adjusting for other tissue changes. A
recent analysis confirmed most beliefs that it is likely that changes in the subchondral
bone and synovial activation/ effusion predominate (28).

Lesions in the bone marrow play an integral if not pivotal role in the symptoms that
emanate from knee OA and its structural progression (23). Bone marrow lesions were
found in 272 of 351 (77.5%) persons with painful knees compared with 15 of 50 (30%)
persons with no knee pain (P < 0.001). Large lesions were present almost exclusively in
persons with knee pain (35.9% vs. 2%; P < 0.001). After adjustment for severity of
radiographic disease, effusion, age, and sex, lesions and large lesions remained associated
with the occurrence of knee pain. More recently their relation to pain severity was also
demonstrated (24). Other bone-related causes of pain include periostitis associated with
osteophyte formation (29), subchondral microfractures (30), and bone angina due to
decreased blood flow and elevated intraosseous pressure (31). The particular bone
pathology most responsible for pain remains elusive however identifying this would be a
major advance in delineating appropriate therapeutic targets. One likely source that
remains underexplored is that of intra-osseous hypertension. The pathophysiology
remains unclear, although phlebographic studies in OA indicate impaired vascular
clearance from bone and raised intra-osseous pressure in the bone marrow near the
painful joint (31–34). What may subsequently cause pain is as yet unknown. Increased
trabecular bone pressure, ischemia and inflammation are all possible stimuli.

The synovial reaction in OA includes synovial hyperplasia, fibrosis, thickening of

synovial capsule, activated synoviocytes and in some cases lymphocytic infiltrate (B- and
T-cells as well as plasma cells) (35). The site of infiltration of the synovium is of obvious
relevance as one of the most densely innervated structures of the joint is the white
adipose tissue of the fat pad which also show evidence of inflammation and can act as a
rich source of inflammatory adipokines (36). 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, proteinases,
neuropeptides and cytokines (37;38). Synovitis is frequently present in osteoarthritis and
may predict other structural changes in osteoarthritis and correlate with pain and other
clinical outcomes (26). Synovial thickening around the infra-patellar fat pad using non-
contrast MRI has been shown on biopsy to represent mild chronic synovitis (39). A semi-
quantitative measure of synovitis from the infrapatellar fat pad is associated with pain
severity and similarly change in synovitis is associated with change in pain severity (27).

Another source of joint pain in OA may be from the nerves themselves. Following joint
injury in which there is ligamentous rupture, the nerves which re-innervate the healing
soft tissues contain an overabundance of algesic chemicals such as substance P and
calcitonin gene-related peptide. An interesting observation of these new nerves was that
their overall morphology was abnormal with fibres appearing punctate and disorganised
(40;41). Since these phenomena are consistent with the innervation profiles described in
nerve injury models, we speculate that injured joints may develop neuropathic pain post-
trauma. Indeed, treatment of inflamed joints with the neuropathic pain analgesic
gabapentin can also relieve arthritis pain (42).

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Innervation in the Joint

The musculature, articular capsule, synovium, tendons, ligaments, and subchondral bone
of the joint have a rich nerve supply, whereas the articular hyaline cartilage is aneural. In
addition to post-ganglionic sympathetic efferents, joints are supplied by numerous
sensory fibres whose subcategorization is based upon distinct anatomical features (43).
Joint afferents which have a thick diameter and are myelinated are called Aβ (Group II)
fibres, thin nerves with a myelin sheath which disappears in the terminal region to
become a free nerve ending are termed Aδ (Group III) fibres, while the thin unmyelinated
nerves are C (Group IV) fibres. Proprioceptive Aβ fibres of the joint terminate in the
capsule, fat pad, ligaments, menisci and periosteum, whilst nociceptive Aδ and C fibres
innervate the capsule, ligaments, menisci, periosteum and mineralised bone, (in particular
in regions of high mechanical load) (37;43–45).

Joint nociceptors are typically localised within specific articular structures and their
receptive field is normally restricted to the joint. During inflammation, however, this
receptive field can expand into adjacent areas such that mechanical stimuli in non-
articular tissues such as the surrounding muscle can suddenly become activated.
Therefore, a typical neurone in the spinal cord with a receptive field in the joint may now
respond to physical stimulation of extra-articular muscle for example (46;47).
Under disease conditions, the innervation territories of the various nerve fibers are highly
plastic. An example of such plasticity, is the innervation of normally aneural tissues such
as cartilage with substance P and calcitonin-gene-related peptide (CGRP) positive nerves
in patients with OA (48). Therefore, the "normally" mechanically insensitive cartilage
becomes potentially a candidate for tibiofemoral pain in OA although this has never been
shown electrophysiologically. Furthermore, these peptide-containing nerves may also
accelerate disease progression via localized neurogenic inflammatory mechanisms.

Tissue injury activates the nociceptive system, which generates the subjective pain
experience. Spontaneous pain and mechanical hypersensitivity can develop as a
consequence of sensitization of primary afferents directly by locally released
inflammatory mediators, as well as following sensitization of neuronal processes in the
spinal cord (central sensitization) or indeed higher centres (46).

In arthritis, inflammatory mediators such as bradykinin, histamine, prostaglandins, lactic

acid, substance P, vasoactive intestinal peptide and calcitonin gene related peptide
(CGRP) are released into the joint (38). These mediators reduce the firing threshold of
joint nociceptors, making them more likely to respond to both non-noxious and noxious
painful stimuli. As the disease progresses, more and more of these mediators accumulate
in the joint, thereby triggering a self-perpetuating cycle of pain generation. The first study
to explore which chemical mediators are responsible for OA pain in an animal model
focused on the neuropeptide vasoactive intestinal peptide (VIP). VIP is a 28 amino acid
peptide which was originally identified in the porcine intestine where it controls vascular
tone and enzyme secretion (49). Over 20 years ago, VIP was localised in the synovial
fluid and serum of arthritis patients (50) and then the peptide was forgotten by the
rheumatology field. Recently it was shown that local administration of VIP to rat knees
causes synovial hyperaemia (51) and sensitization of joint afferents leading to pain
(52;53). Interestingly, treatment of OA knees with a VIP antagonist significantly
attenuated peripheral sensitization and alleviated pain behaviour in this animal model of
degenerative joint disease. Thus, VIP inhibition may be a useful means of controlling OA
pain.

In addition to sensitizing mediators being released into OA joints to elicit pain, evidence
is beginning to emerge which suggests that naturally produced desensitizing agents may
also contribute to pain modulation in the joint. For example, the endogenous opioid
endomorphin is present in high concentration in arthritic knees (54;55) where it can
reduce afferent firing rate in response to joint movement (56). Similarly, endocannabinoid
activity has been reported in OA knees and activation of the articular cannabinoid system
can dramatically offset the hyperactivity of joint nociceptors (57). Even though these
endogenous analgesic agents are present in significant amounts in articular tissues, the
question still remains as to why the body's natural pain killers are unable to provide any
appreciable relief from the debilitating effects of joint pain.

Silent Nociceptors
Polymodal Aδ and C fibers that innervate the joint increase their firing rate in response to
noxious mechanical stimuli as well as in the presence of various chemical agents such as
those released during inflammation. In addition to these classic nociceptors, there are also
a number of fibers in the joint that are not normally activated by noxious stimulation but
become responsive when damage or inflammation occurs in the joint. These fibers, called
silent nociceptors, can make a major contribution to the pain sensation (46).

The neuroanatomy of mineralized bone, bone marrow and periosteum is well defined
(45). A-β, A-δ, C-fibers and sympathetic fibers distribute densely throughout the
periosteum, entering bone in close association with blood vessels (58). Of these tissues,
the periosteum has the greatest density of sensory and sympathetic innervation, which
may be further enhanced during joint inflammation. Electrophysiological studies of the
mechano-sensitivity of joint innervation, indicate that generally A-β fibres are activated
by non-noxious normal working range joint movement whilst approximately 50% of A-δ
and 70% of C-fibers are classified as high threshold units (59). During inflammation, A-δ
and C-fibers show increased mechano-sensitivity. Low threshold populations exhibit
exaggerated responses, whilst high threshold populations and units that were initially
mechano-insensitive are sensitized and now respond to movements in the normal
working ranges of the joint (60). It is this increased activity of low threshold units and the
awakening of the silent nociceptors which conspire to intensify joint pain sensation in
arthritis.

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Central Mechanisms
The A-δ fibers transmit impulses centrally through the peripheral nerve up through the
dorsal root and into the dorsal horn of the spinal cord. The C fibers conduct impulses
relatively slowly through the same route to the central nervous system (CNS) (61) (See
Figure 2). The A-δ fibers terminate in laminae I and V of the dorsal horn, and the C fibers
terminate predominantly in lamina II. From the dorsal horn, the signals are carried along
the ascending pain pathways to the brain stem, hypothalamus, thalamus, and cerebral
cortex.

Figure 2
Pain transmission. Reproduced with permission from Schaible H-G et al. (44)

Descending pathways originating in supraspinal centers (somatosensory and limbic

cortices) project through the periaqueductal gray area to the dorsal horn and modulate
activity in the dorsal horn by controlling spinal pain transmission (62).
Processing the Perception of Pain

Nociception is processed throughout the nervous system, but it reaches conscious levels
and is interpreted through connections between the thalamus and cortex. There are 2 main
systems in the brain that are responsible for the perception of pain: the lateral system and
the medial system of the lateral spinothalamic tract (63). The lateral system involves the
activation of thalamic nuclei in the ventral lateral thalamus and the relay of information
to the somatosensory cortex, where the noxious stimulus is analyzed for location,
duration, intensity, and quality.

The medial system involves the relay of information by other (midline and intralaminar)
thalamic nuclei to different parts of the brain such as the amygdala. The medial system
comprises large areas of the brain that are responsible for pain perception as well as for
functions in other contexts, such as affective responses, attention, and learning. This may
explain the discrepancy between the degree of joint damage and the severity of pain.
Because of the importance of the medial system in OA pain, a non-pharmacologic
approach to management may be just as important as a pharmacologic strategy.

Finally, the perception of pain is modified by the patient’s affective status (e.g. level of
depression, anxiety, or anger) and cognitive state (e.g. pain beliefs, expectations,
memories of pain). Age, gender, socioeconomic status, racial and cultural background,
pain communication skills, and previous pain experiences can contribute to the way a
patient perceives pain.

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Central Sensitization
The characteristic feature of most chronic pains is that hitherto non-noxious stimuli, such
as walking or standing, are perceived as painful. It is now clear that pain pathways, far
from being static or hardwired, exhibit marked plasticity and that sensitization at
peripheral, spinal and cortical levels accounts for many of the clinical features associated
with chronic pain. Consistent with this, the three chronic pain categories currently
recognised, including neuropathic pain, neuroplastic or inflammatory pain and idiopathic
pain, all exhibit features of an underlying central sensitization state (38).

Like peripheral sensitization previously described, central nociceptive transmission in the

dorsal horn also can be sensitized. Increased input from peripheral nociceptors modulates
spinal cord pain-transmitting neurons and leads to increased synaptic excitability and
decreased firing thresholds that outlast the initiating input, amplifying responses to both
noxious and innocuous inputs.

Thus, neuronal responses to noxious input is exaggerated (hyperalgesia), or normally

innocuous input is now perceived as painful (allodynia), and sensitivity is expanded, with
pain experienced beyond the original site of tissue damage (secondary hyperalgesia) (64).
Central sensitization involves activation and modulation, as well as modification.
Modification of dorsal horn neurons leads to changes in receptors and transmitters in
addition to structural reorganization (or physical rearrangement of the neurons) and
disinhibition of dorsal horn nociceptors. According to one theory, disinhibition of dorsal
horn nociceptors results from the death of local inhibitory interneurons, which potentially
are replaced by excitatory A-δδ̣ fibers that “sprout” from the dorsal horn. Peripheral and
central sensitization represent the “plasticity,” or modifiability, of the nervous system,
which can mold itself to new functions in response to changing inputs (38;64).

Hyperexcitability of Spinal Cord Neurons

Spinal cord hyperexcitability can originate from either nociceptive or neuropathic types
of pain, though the mechanisms through which this occurs may be different (65). When a
noxious stimulus is used to induce active inflammation, the sensitized area expands and
additional neurons become activated. This process lowers the pain threshold and
increases the sensitivity of adjacent neurons to stimulation (65). Central sensitization
occurs as a consequence of tissue damage and peripheral sensitization and also as a
consequence of abnormal discharges from damaged nerve fibers. A spinal cord neuron
that has been sensitized often has an expanded receptive field. In addition, as a result of
the process of central sensitization, more neurons in a spinal segment respond to noxious
stimuli. Central sensitization has been seen mainly in the wake of tissue damage. In some
forms of neuropathy, eg, after sectioning of peripheral nerves, many spinal cord neurons
are silent and have no receptive field. Only a few neurons are active and show abnormal
discharges. Other parts of the CNS also have the capacity for plasticity: After
denervation, cortical maps may be changed, and this cortical process may be responsible
for the chronicity of pain. It is this plastic quality of the central nervous system which
should enable us to reverse chronic pain in long term diseases such as OA. By inhibiting
the nociceptive input from the joint to the central nervous system it should be possible to
rewire the brain gradually such that the sensation of chronic joint pain can be unlearned.
Peripherally restricted pharmacological agents perhaps in combination with a physical
therapy approach may help us ultimately to dismantle the neurophysiological processes
which were constructed during OA pain development.

Modulatory Mediators

Glutamate is the primary excitatory neurotransmitter in the CNS. It is the

neurotransmitter in A-β, A-δ, and C fibers. During repetitive noxious stimulation,
glutamate activates N-methyl- D-aspartate (NMDA) in the spinal cord, and neuropeptide
receptors are activated by neuropeptides that are co-released with glutamate from
synaptic endings (65). Additionally, many modulatory mediators are present, including
substance P, CGRP, opioids, neurotrophins, and prostaglandins, all of which also act in
the CNS. Substance P, which is released in the superficial part of the dorsal horn into the
gray matter, increases the pain response to noxious inputs from spinal cord neurons (66).

Prostaglandins are also important, both in the periphery and in the spinal cord. They have
a major impact on the sensitivity of neighboring spinal cord neurons (67).
The Concept of Wind Up

When action potentials reach the nerve terminal, the presynaptic membrane is
depolarized. This opens calcium channels, and calcium flows into the presynaptic ending,
where it triggers the release of transmitters. The definition of wind up is quite specific: In
a classic situation, a peripheral nerve is stimulated repeatedly at C-fiber strength. This
produces a response in a spinal neuron that grows from stimulus to stimulus; this is
termed wind up. Wind up is short-lived, surviving stimulation for only a very short time
(seconds to minutes). Wind up intensifies pain during repetitive noxious stimulation. It is
probably not produced by increased transmitter release but rather by postsynaptic
changes such as NMDA receptor activation and, possibly, by calcium influx into the
postsynaptic neuron. Wind up also occurs when the skin is stimulated repeatedly with
short heat pulses (65).

The Sympathetic Response

When a noxious stimulus is received, the sympathetic nervous system releases

norepinephrine into the peripheral tissues, which decreases the firing threshold of
peripheral nerve cells and makes them more sensitive to stimulation. During noxious
painful movement, sympathetic postganglionic nerve activity increases leading to a rise
in mean arterial pressure and heart rate (68). Since sympathetic nerve stimulation leads to
synovial vasoconstriction (69), then it is possible that the resulting hypoxemia could
contribute to joint pain. These findings indicate that activation of joint
mechanonociceptors causes reflex sympathetic discharges which could further augment
joint pain sensitivity.

So far this review has focused on peripheral sensory input and central mechanisms
although clearly modulation through cognitive, genetic, affective and environmental
influences forms the net pain experience. The remainder of the review will focus on
constitutional and environmental factors that may modulate the pain experience.

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Constitutional factors
Pain has long been recognized as a complex sensory and emotional experience (70). Each
individual has a unique experience of pain influenced by their life experience and
genotypic profile. An individual’s stable psychological characteristics (trait) and the
immediate psychological context in which pain is experienced (state) both influence
perception of pain.

A full understanding of pain requires consideration of psychological and social

environmental processes mediating a patient’s response to their disease (71). The
biopsychosocial model is a very useful approach to understanding and assessing the
experience of pain in persons with OA (72). Numerous studies have supported the
importance of psychological factors in understanding OA pain (72). Two of the most
important factors are self-efficacy and pain catastrophizing. Self-efficacy has been
defined as an individuals confidence in their abilities to accomplish a desired task (e.g.
control arthritis pain). Keefe, Lefebvre, et al. (73) found that OA patients who reported
higher self-efficacy for pain control had higher thresholds and tolerance for thermal pain
stimuli. Furthermore, increases in self-efficacy occurring over the course of a pain coping
skills training protocol for OA patients was found to be one of the most important
predictors of short- and long-term treatment outcome (74;75). In fact, Lorig et al, (76)
found that increases in self-efficacy that occured following participation in an arthritis
self-help intervention were related to improvements in pain and psychological
functioning at 4 years follow-up. Pain catastrophizing refers to the tendency to focus
upon, ruminate upon, and feel helpless in the face of pain. OA patients who catastrophize
report higher levels of pain, psychological distress, and physical disability and also
exhibit more pain behavior (77). Interestingly, pain catastrophizing has also been shown
to relate to abnormal processing of pain signals in imaging studies suggesting it may
influence pain perception in a fundamental fashion (78).

OA pain occurs in a social context and factors such as social support can play an
important role in determining how patients adjust to arthritis pain (79). Patients and their
partners, however, may vary with respect to their abilities to communicate about and
manage OA pain as a couple. In a recent study, (80), we examined key aspects of pain
communication (self-efficacy for pain communication and holding back from discussing
pain and arthritis-related concerns) in patients with osteoarthritis (OA) and their partners.
Results indicated that patients who reported higher levels of self-efficacy for pain
communication experienced much lower levels of pain, physical and psychological
disability, and their partners reported much lower levels of negative affect. Patients who
reported holding back on discussions about pain and related arthritis concerns
experienced much higher levels of psychological disability. Interestingly, when partners
reported they held back on discussions of pain and related arthritis concerns, they
reported higher levels of caregiver strain and their patient-partners were more likely to
report high levels of psychological disability. Taken together, these findings suggest that
patients' and partners' self-efficacy for pain communication and tendency to hold back on
pain communication may be important in understanding patient and partner adjustment to
OA pain. These findings also underscore the importance of involving spouses of OA
patients in pain management efforts, something that has been shown to improve the
outcomes of pain coping skills training (74;75).

Further, central nervous system processing associated with pain perception is closely
integrated with hypothalamic-pituitary axis (HPA) and autonomic nervous system (ANS)
activity. Variations in pain perception within populations may reflect genetic
polymorphisms in all three systems, with current attention being focused on serotonin
transporter re-uptake protein (SERT-P), Alpha-2 receptor and catechol-O-
methyltransferase (COMT) although a number of other candidate genes are under review
(45).

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Environmental stimuli
In the presence of OA local stimuli that typically would not be noxious can precipitate
alteration in the severity of pain through either micro-structural damage of the joint or by
decreasing the pain threshold level. There is evidence that patients with OA do
experience fluctuations in pain severity or exacerbations of pain (26;81). A brief
consideration of some of the factors that could predispose to fluctuations in pain severity
are discussed here.

I. Physical activity

Numerous studies have assessed the relation of physical activity to the risk of
radiographic knee OA with little or no attention paid to the relation of physical activity
and OA symptoms. These include studies of runners (82–84), heavy physical activity in
daily life (85), and occupational activities including prolonged standing and knee bending
activities (86–89) however few if any of these studies have investigated the relation of
these activities to symptom severity. In fact there is a paucity of epidemiological data to
explain which particular activities are painful or more injurious than others however we
know from clinical practice that different activities predispose to exacerbation of pain
where in a normal joint they typically would not. Identification of these factors that
exacerbate pain is important as these are potentially modifiable.

II. Foot wear

Appropriate supportive footwear is recommended in guidelines for treating symptomatic

OA although there is little data to support this recommendation (90). There are a number
of ways in which footwear can potentially modify impact loading through the lower limb
and thus reduce impact that potentially may lead to pain in subjects with OA. Impact
force during locomotion increases with increasing age as a function of diminishing foot
position awareness (91); this impact force could be reduced through the addition of
supportive shoes (92).

Another link between footwear and knee loads comes from gait analysis studies
demonstrating that high- heeled shoes increase compressive forces across the
patellofemoral and medial tibiofemoral joints (93). Women’s shoes, even with only
moderately high heels (1.5 in) were found to increase the forces that strain both the
tibiofemoral and patellofemoral joints during walking (94). Given the increased
predilection for women experiencing symptomatic knee OA (female to male ratio is
typically reported as 2:1) clarifying the impact high heeled shoes have on symptoms
could have public health import.

III. Injury and Trauma

Among both genders, a past history of injury to the stabilizing or load bearing structures
of the knee renders the joint highly vulnerable to radiographic OA in subsequent years
(95). Persons with OA have quadriceps weakness (96) and impaired proprioception (97)
that makes them more susceptible to falls (98) and injury risk. In contrast to the
knowledge about the development of radiographic OA following injury, the relationship
of pain exacerbation in subjects with pre-existing OA to joint injury/falls/ trauma remains
unknown and warrants further exploration.

IV. Weather

Many people believe that weather conditions can influence joint pain, but science offers
little proof (99;100). If the phenomenon were real, cause-and-effect mechanisms might
provide clues that would aid treatment of joint pain. Some theorize that alterations in
barometric pressure and humidity can alter the synovial fluid (volume and content) in the
joint and predispose to alteration in symptoms. The factors that have been considered
include ambient temperature, barometric pressure, relative humidity, sunshine, wind
speed and precipitation; however the literature on the subject is sparse, conflicting, and
vulnerable to bias (101;102). However, for patients who believe that weather can
influence their pain, the biological mechanisms may not be fully understood, but the
effect seems to be real.

Go to:

Conclusion
The pathophysiology of pain in OA is complex and similarly the symptomatic
presentation in OA diverse and heterogeneous. Attention to the many modulating factors
that alter the experience of pain may improve the way we treat this disease.

Go to:

Acknowledgements
Preparation of this article for Francis Keefe was supported in part by NIH grants:
AG026010, AR47218, AR049059, AR050245, and AR05462.

Go to:

Footnotes
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version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final citable form. Please note
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Go to:

Reference List
1. Guccione AA, Felson DT, Anderson JJ, Anthony JM, Zhang Y, Wilson PW, et al. The
effects of specific medical conditions on the functional limitations of elders in the
Framingham Study. American Journal of Public Health. 1994;84(3):351–358. [PMC free
article] [PubMed]
2. Arthritis prevalence and activity limitations--United States, 1990. MMWR - Morbidity
& Mortality Weekly Report. 1994;43(24):433–438. [PubMed]
3. Yelin E, Callahan LF. The economic cost and social and psychological impact of
musculoskeletal conditions. National Arthritis Data Work Groups. Arthritis &
Rheumatism. 1995;38(10):1351–1362. [see comments] [Review] [68 refs]. [PubMed]
4. Segal L, Day SE, Chapman AB, Osborne RH. Can we reduce disease burden from
osteoarthritis? Medical Journal of Australia. 2004;180(5 Suppl):S11–S17. [see comment].
[PubMed]
5. Nuki G. Osteoarthritis: a problem of joint failure. Zeitschrift fur Rheumatologie.
1999;58(3):142–147. [Review] [55 refs]. [PubMed]
6. Eyre DR. Collagens and cartilage matrix homeostasis. Clinical Orthopaedics & Related
Research. 2004;(427 Suppl):S118–S122. [Review] [37 refs]. [PubMed]
7. Hannan MT, Felson DT, Pincus T. Analysis of the discordance between radiographic
changes and knee pain in osteoarthritis of the knee. Journal of Rheumatology.
2000;27(6):1513–1517. [PubMed]
8. Peat G, McCarney R, Croft P. Knee pain and osteoarthritis in older adults: a review of
community burden and current use of primary health care. Annals of the Rheumatic
Diseases. 2001;60(2):91–97. [see comments.]. [Review] [45 refs]. [PMC free article]
[PubMed]
9. Cibere J. Do we need radiographs to diagnose osteoarthritis? Best Practice & Research
in Clinical Rheumatology. 2006;20(1):27–38. [Review] [60 refs]. [PubMed]
10. Zhang Y, Niu J, Kelly-Hayes M, Chaisson CE, Aliabadi P, Felson DT. Prevalence of
symptomatic hand osteoarthritis and its impact on functional status among the elderly:
The Framingham Study. American Journal of Epidemiology. 2002;156(11):1021–1027.
[PubMed]
11. Cunningham LS, Kelsey JL. Epidemiology of musculoskeletal impairments and
associated disability. American Journal of Public Health. 1984;74(6):574–579. [PMC free
article] [PubMed]
12. Armstrong AL, Hunter JB, Davis TR. The prevalence of degenerative arthritis of the
base of the thumb in post-menopausal women. Journal of Hand Surgery - British Volume.
1994;19(3):340–341. [PubMed]
13. Felson DT, Zhang Y. An update on the epidemiology of knee and hip osteoarthritis
with a view to prevention. Arthritis & Rheumatism. 1998;41(8):1343–1355. [Review]
[116 refs]. [PubMed]
14. Nevitt MC, Xu L, Zhang Y, Lui LY, Yu W, Lane NE, 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 & Rheumatism.
2002;46(7):1773–1779. [PubMed]
15. Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH, et al.
Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the
United States. Arthritis & Rheumatism. 1998;41(5):778–799. [see comments.]. [PubMed]
16. Kraus VB, Vail TP, Worrell T, McDaniel G, Kraus VB, Vail TP, et al. A comparative
assessment of alignment angle of the knee by radiographic and physical examination
methods. Arthritis & Rheumatism. 2005;52(6):1730–1735. [PubMed]
17. Altman RD. Classification of disease: osteoarthritis. Seminars in Arthritis &
Rheumatism. 1991;20 6 Suppl 2:40–47. [Review] [38 refs]. [PubMed]
18. Bhattacharyya T, Gale D, Dewire P, Totterman S, Gale ME, McLaughlin S, et al. The
clinical importance of meniscal tears demonstrated by magnetic resonance imaging in
osteoarthritis of the knee. Journal of Bone & Joint Surgery - American Volume. 2003;85-
A(1):4–9. [comment]. [PubMed]
19. Englund M, Lohmander LS. Risk factors for symptomatic knee osteoarthritis fifteen
to twenty-two years after meniscectomy. Arthritis & Rheumatism. 2004;50(9):2811–
2819. [PubMed]
20. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, 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 & Rheumatism. 1986;29(8):1039–1049. [PubMed]
21. Dieppe PA, Lohmander LS. Pathogenesis and management of pain in osteoarthritis.
Lancet. 2005;365(9463):965–973. [Review] [100 refs]. [PubMed]
22. Felson D. The sources of pain in knee osteoarthritis. Current Opinion in
Rheumatology. 2005;17(5):624–628. [Review] [34 refs]. [PubMed]
23. Felson DT, Chaisson CE, Hill CL, Totterman SM, Gale ME, Skinner KM, et al. The
association of bone marrow lesions with pain in knee osteoarthritis. Annals of Internal
Medicine. 2001;134(7):541–549. [see comments.]. [PubMed]
24. Hunter D, Gale D, Grainger G, Lo G, Conaghan P. The reliability of a new scoring
system for knee osteoarthritis MRI and the validity of bone marrow lesion assessment:
BLOKS (Boston Leeds Osteoarthritis Knee Score) Annals of the Rheumatic Diseases.
2008;67(2):206–211. [PubMed]
25. Torres L, Dunlop DD, Peterfy C, Guermazi A, Prasad P, Hayes KW, et al. The
relationship between specific tissue lesions and pain severity in persons with knee
osteoarthritis. Osteoarthritis & Cartilage. 2006;14(10):1033–1040. [PubMed]
26. Hill CL, Gale DG, Chaisson CE, Skinner K, Kazis L, Gale ME, et al. Knee effusions,
popliteal cysts, and synovial thickening: association with knee pain in osteoarthritis.
Journalof Rheumatology. 2001;28(6):1330–1337. [PubMed]
27. Hill CL, Hunter DJ, Niu J, Clancy M, Guermazi A, Genant H, et al. Changes in
synovitis are associated with changes in pain in knee osteoarthritis. Arthritis &
Rheumatism. 2005;52(9) supplement:S71. Ref Type: Abstract.
28. Lo G, McAlindon T, Niu J, Zhang Y, Beals C, Dabrowski C, et al. Strong Association
of Bone Marrow Lesions and Effusion with Pain in Osteoarthritis. Arthritis &
Rheumatism. 2008;56(9):S790. Ref Type: Abstract.
29. Cicuttini FM, Baker J, Hart DJ, Spector TD. Association of pain with radiological
changes in different compartments and views of the knee joint. Osteoarthritis &
Cartilage. 1996;4(2):143–147. [PubMed]
30. Burr DB. The importance of subchondral bone in the progression of osteoarthritis.
Journal of Rheumatology - supplement. 2004;70:77–80. [Review] [13 refs]. [PubMed]
31. Simkin P. Bone pain and pressure in osteoarthritic joints. Novartis Foundation
Symposium. 2004;260:179–186. [Review] [34 refs]. [PubMed]
32. Arnoldi CC, Lemperg K, Linderholm H. Intraosseous hypertension and pain in the
knee. Journal of Bone & Joint Surgery - British Volume. 1975;57(3):360–363. [PubMed]
33. Arnoldi CC, Djurhuus JC, Heerfordt J, Karle A. Intraosseous phlebography,
intraosseous pressure measurements and 99mTC-polyphosphate scintigraphy in patients
with various painful conditions in the hip and knee. Acta Orthopaedica Scandinavica.
1980;51(1):19–28. [PubMed]
34. Arnoldi CC. Vascular aspects of degenerative joint disorders. A synthesis. Acta
Orthopaedica Scandinavica. 1994;261 Supplementum:1–82. [Review] [270 refs].
[PubMed]
35. Roach HI, Aigner T, Soder S, Haag J, Welkerling H, Roach HI, et al. Pathobiology of
osteoarthritis: pathomechanisms and potential therapeutic targets. Current Drug Targets.
2007;8(2):271–282. [Review] [138 refs]. [PubMed]
36. Ushiyama T, Chano T, Inoue K, Matsusue Y, Ushiyama T, Chano T, et al. Cytokine
production in the infrapatellar fat pad: another source of cytokines in knee synovial
fluids. Annals of the Rheumatic Diseases. 2003;62(2):108–112. [PMC free article]
[PubMed]
37. McDougall J. Arthritis and pain. Neurogenic origin of joint pain. Arthritis Research &
Therapy. 2006;8(6):220. [Review] [138 refs]. [PMC free article] [PubMed]
38. Altman R. Management of Osteoarthritis Knee Pain: The State of the Science.
Littleton, CO: Medical Education Resources; 2006. Ref Type: Report.
39. Fernandez-Madrid F, Karvonen RL, Teitge RA, Miller PR, An T, Negendank WG.
Synovial thickening detected by MR imaging in osteoarthritis of the knee confirmed by
biopsy as synovitis. Magnetic Resonance Imaging. 1995;13(2):177–183. [PubMed]
40. McDougall JJ, Bray RC, Sharkey KA. Morphological and immunohistochemical
examination of nerves in normal and injured collateral ligaments of rat, rabbit, and
human knee joints. Anatomical Record. 1997;248(1):29–39. [PubMed]
41. McDougall JJ, Yeung G, Leonard CA, Bray RC. A role for calcitonin gene-related
peptide in rabbit knee joint ligament healing. Canadian Journal of Physiology &
Pharmacology. 2000;78(7):535–540. [PubMed]
42. Hanesch U, Pawlak M, McDougall JJ, Hanesch U, Pawlak M, McDougall JJ.
Gabapentin reduces the mechanosensitivity of fine afferent nerve fibres in normal and
inflamed rat knee joints. Pain. 2003;104(1–2):363–366. [PubMed]
43. Freeman MA, Wyke B. The innervation of the knee joint. An anatomical and
histological study in the cat. Journal of Anatomy. 1967;101(Pt 3):505–532. [PMC free
article] [PubMed]
44. Schaible H, Richter F. Pathophysiology of pain. Langenbecks Archives of Surgery.
2004;389(4):237–243. [Review] [55 refs]. [PubMed]
45. Dray A, Read SJ, Dray A, Read SJ. Arthritis and pain. Future targets to control
osteoarthritis pain. Arthritis Research & Therapy. 2007;9(3):212. [Review] [176 refs].
[PMC free article] [PubMed]
46. Schaible H, Schmelz M, Tegeder I. Pathophysiology and treatment of pain in joint
disease. Advanced Drug Delivery Reviews. 2006;58(2):323–342. [Review] [226 refs].
[PubMed]
47. Konttinen YT, Kemppinen P, Segerberg M, Hukkanen M, Rees R, Santavirta S, et al.
Peripheral and spinal neural mechanisms in arthritis, with particular reference to
treatment of inflammation and pain. Arthritis & Rheumatism. 1994;37(7):965–982.
[Review] [55 refs]. [PubMed]
48. Suri S, Gill SE, Massena dC, Wilson D, McWilliams DF, Walsh DA, et al.
Neurovascular invasion at the osteochondral junction and in osteophytes in osteoarthritis.
Annals of the Rheumatic Diseases. 2007;66(11):1423–1428. [PMC free article]
[PubMed]
49. Said S, Mutt V. Polypeptide with broad biological activity: isolation from small
intestine. Science. 1970;169(951):1217–1218. [PubMed]
50. Lygren I, Ostensen M, Burhol PG, Husby G, Lygren I, Ostensen M, et al.
Gastrointestinal peptides in serum and synovial fluid from patients with inflammatory
joint disease. Annals of the Rheumatic Diseases. 1986;45(8):637–640. [PMC free article]
[PubMed]
51. McDougall JJ, Barin AK. The role of joint nerves and mast cells in the alteration of
vasoactive intestinal peptide (VIP) sensitivity during inflammation progression in rats.
British Journal of Pharmacology. 2005;145(1):104–113. [PMC free article] [PubMed]
52. Schuelert N, McDougall JJ, Schuelert N, McDougall JJ. Electrophysiological
evidence that the vasoactive intestinal peptide receptor antagonist VIP6-28 reduces
nociception in an animal model of osteoarthritis. Osteoarthritis & Cartilage.
2006;14(11):1155–1162. [PubMed]
53. McDougall JJ, Watkins L, Li Z. Vasoactive intestinal peptide (VIP) is a modulator of
joint pain in a rat model of osteoarthritis. Pain. 2006;123(1–2):98–105. [PubMed]
54. McDougall JJ, Baker CL, Hermann PM. Attenuation of knee joint inflammation by
peripherally administered endomorphin-1. Journal of Molecular Neuroscience.
2004;22(1–2):125–137. [PubMed]
55. McDougall JJ, Barin AK, McDougall CM. Loss of vasomotor responsiveness to the
mu-opioid receptor ligand endomorphin-1 in adjuvant monoarthritic rat knee joints.
American Journal of Physiology - Regulatory Integrative & Comparative Physiology.
2004;286(4):R634–R641. [PubMed]
56. Li Z, Proud D, Zhang C, Wiehler S, McDougall JJ, Li Z, et al. Chronic arthritis down-
regulates peripheral mu-opioid receptor expression with concomitant loss of
endomorphin 1 antinociception. Arthritis & Rheumatism. 2005;52(10):3210–3219. [see
comment]. [PubMed]
57. Schuelert N, McDougall JJ, Schuelert N, McDougall JJ. Cannabinoid-mediated
antinociception is enhanced in rat osteoarthritic knees. Arthritis & Rheumatism.
2008;58(1):145–153. [PubMed]
58. Mach DB, Rogers SD, Sabino MC, Luger NM, Schwei MJ, Pomonis JD, et al.
Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur.
Neuroscience. 2002;113(1):155–166. [PubMed]
59. Schaible HG, Grubb BD. Afferent and spinal mechanisms of joint pain. Pain.
1993;55(1):5–54. [Review] [438 refs]. [PubMed]
60. Schaible HG, Schmidt RF, Schaible HG, Schmidt RF. Effects of an experimental
arthritis on the sensory properties of fine articular afferent units. Journal of
Neurophysiology. 1985;54(5):1109–1122. [PubMed]
61. Schwartzman RJ, Grothusen J, Kiefer TR, Rohr P, Schwartzman RJ, Grothusen J, et
al. Neuropathic central pain: epidemiology, etiology, and treatment options. Archives of
Neurology. 2001;58(10):1547–1550. [Review] [38 refs]. [PubMed]
62. Basbaum AI. Spinal mechanisms of acute and persistent pain. Regional Anesthesia &
Pain Medicine. 1999;24(1):59–67. [Review] [46 refs]. [PubMed]
63. Treede RD, Kenshalo DR, Gracely RH, Jones AK, Treede RD, Kenshalo DR, et al.
The cortical representation of pain. Pain. 1999;79(2–3):105–111. [see comment].
[Review] [58 refs]. [PubMed]
64. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science.
2000;288(5472):1765–1769. [Review] [73 refs]. [PubMed]
65. Ollat H, Cesaro P. Pharmacology of neuropathic pain. Clinical Neuropharmacology.
1995;18(5):391–404. [Review] [62 refs]. [PubMed]
66. Joshi GP, Ogunnaike BO. Consequences of inadequate postoperative pain relief and
chronic persistent postoperative pain. Anesthesiology Clinics of North America.
2005;23(1):21–36. [Review] [94 refs]. [PubMed]
67. Samad TA, Moore KA, Sapirstein A, Billet S, Allchorne A, Poole S, et al. Interleukin-
1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain
hypersensitivity. Nature. 2001;410(6827):471–475. [see comment]. [PubMed]
68. Sato Y, Schaible HG. Discharge characteristics of sympathetic efferents to the knee
joint of the cat. Journal of the Autonomic Nervous System. 1987;19(2):95–103.
[PubMed]
69. McDougall J, Karimian SM, Ferrell WR. Prolonged alteration of vasoconstrictor and
vasodilator responses in rat knee joints by adjuvant monoarthritis. Experimental
Physiology. 1995;80(3):349–357. [PubMed]
70. Kane RL, Bershadsky B, Lin WC, Rockwood T, Wood K, Kane RL, et al. Efforts to
standardize the reporting of pain. Journal of Clinical Epidemiology. 2002;55(2):105–110.
[PubMed]
71. Orbell S, Johnston M, Rowley D, Espley A, Davey P. Cognitive representations of
illness and functional and affective adjustment following surgery for osteoarthritis. Social
Science & Medicine. 1998;47(1):93–102. [PubMed]
72. Keefe FJ, Smith SJ, Buffington AL, Gibson J, Studts JL, Caldwell DS. Recent
advances and future directions in the biopsychosocial assessment and treatment of
arthritis. Journal of Consulting & Clinical Psychology. 2002;70(3):640–655. [Review]
[126 refs]. [PubMed]
73. Keefe FJ, Lefebvre JC, Maixner W, Salley AN, Jr, Caldwell DS, Keefe FJ, et al. Self-
efficacy for arthritis pain: relationship to perception of thermal laboratory pain stimuli.
Arthritis Care & Research. 1997;10(3):177–184. [PubMed]
74. Keefe FJ, Caldwell DS, Baucom D, Salley A, Robinson E, Timmons K, et al. Spouse-
assisted coping skills training in the management of osteoarthritic knee pain. Arthritis
Care & Research. 1996;9(4):279–291. [PubMed]
75. Keefe FJ, Caldwell DS, Baucom D, Salley A, Robinson E, Timmons K, et al. Spouse-
assisted coping skills training in the management of knee pain in osteoarthritis: long-term
followup results. Arthritis Care & Research. 1999;12(2):101–111. [PubMed]
76. Lorig KR, Mazonson PD, Holman HR, Lorig KR, Mazonson PD, Holman HR.
Evidence suggesting that health education for self-management in patients with chronic
arthritis has sustained health benefits while reducing health care costs. Arthritis &
Rheumatism. 1993;36(4):439–446. [PubMed]
77. Keefe FJ, Lefebvre JC, Egert JR, Affleck G, Sullivan MJ, Caldwell DS. The
relationship of gender to pain, pain behavior, and disability in osteoarthritis patients: the
role of catastrophizing. Pain. 2000;87(3):325–334. [PubMed]
78. Seminowicz DA, Davis KD. Cortical responses to pain in healthy individuals depends
on pain catastrophizing. Pain. 2006;120(3):297–306. [PubMed]
79. Penninx BW, van Tilburg T, Deeg DJ, Kriegsman DM, Boeke AJ, van Eijk JT, et al.
Direct and buffer effects of social support and personal coping resources in individuals
with arthritis. Social Science & Medicine. 1997;44(3):393–402. [PubMed]
80. Porter L, Keefe F, Wellington C, Williams A. Pain communication in the context of
osteoarthritis: Patient and partner self-efficacy for pain communication and holding back
from discussion of pain and arthritis-related concerns. Clinical Journal of Pain. In press.
[PubMed]
81. McAlindon T, Formica M, LaValley M, Lehmer M, Kabbara K. Effectiveness of
glucosamine for symptoms of knee osteoarthritis: results from an internet-based
randomized double-blind controlled trial. American Journal of Medicine.
2004;117(9):643–649. [PubMed]
82. Panush RS, Schmidt C, Caldwell JR, Edwards NL, Longley S, Yonker R, et al. Is
running associated with degenerative joint disease? JAMA. 1986;255(9):1152–1154.
[PubMed]
83. Panush R, Hanson C, Caldwell J, Longley S, Stork J, Thoburn R. Is running
associated with osteoarthritis? An eight year follow-up study. J Clin Rheumatol.
1995;1:35–39. Ref Type: Abstract. [PubMed]
84. Lane NE, Michel B, Bjorkengren A, Oehlert J, Shi H, Bloch DA, et al. The risk of
osteoarthritis with running and aging: a 5-year longitudinal study. Journal of
Rheumatology. 1993;20(3):461–468. [PubMed]
85. 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. American Journal of Medicine. 1999;106(2):151–157. [PubMed]
86. Croft P, Cooper C, Wickham C, Coggon D. Osteoarthritis of the hip and occupational
activity. Scandinavian Journal of Work, Environment & Health. 1992;18(1):59–63.
[PubMed]
87. Maetzel A, Makela M, Hawker G, Bombardier C. Osteoarthritis of the hip and knee
and mechanical occupational exposure--a systematic overview of the evidence. Journal of
Rheumatology. 1997;24(8):1599–1607. [PubMed]
88. Felson DT. Do occupation-related physical factors contribute to arthritis? Baillieres
Clinical Rheumatology. 1994;8(1):63–77. [Review] [58 refs]. [PubMed]
89. Vingard E, Alfredsson L, Goldie I, Hogstedt C. Occupation and osteoarthrosis of the
hip and knee: a register-based cohort study. International Journal of Epidemiology.
1991;20(4):1025–1031. [PubMed]
90. Anonymous. Recommendations for the medical management of osteoarthritis of the
hip and knee: 2000 update. American College of Rheumatology Subcommittee on
Osteoarthritis Guidelines. Arthritis & Rheumatism. 2000;43(9):1905–1915. [PubMed]
91. Robbins S, Waked E, Allard P, McClaran J, Krouglicof N. Foot position awareness in
younger and older men: the influence of footwear sole properties. Journal of the
American Geriatrics Society. 1997;45(1):61–66. [PubMed]
92. Robbins S, Waked E, Krouglicof N. Vertical impact increase in middle age may
explain idiopathic weight-bearing joint osteoarthritis. Archives of Physical Medicine &
Rehabilitation. 2001;82(12):1673–1677. [PubMed]
93. Kerrigan DC, Lelas JL, Karvosky ME. Women's shoes and knee osteoarthritis.
Lancet. 2001;357(9262):1097–1098. [PubMed]
94. Kerrigan DC, Johansson JL, Bryant MG, Boxer JA, Croce UD, Riley PO, et al.
Moderate-heeled shoes and knee joint torques relevant to the development and
progression of knee osteoarthritis. Archives of Physical Medicine & Rehabilitation.
2005;86(5):871–875. [PubMed]
95. Davis MA, Ettinger WH, Neuhaus JM, Cho SA, Hauck WW. The association of knee
injury and obesity with unilateral and bilateral osteoarthritis of the knee. American
Journal of Epidemiology. 1989;130(2):278–288. [PubMed]
96. Slemenda C, Brandt KD, Heilman DK, Mazzuca S, Braunstein EM, Katz BP, et al.
Quadriceps weakness and osteoarthritis of the knee. Annals of Internal Medicine.
1997;127(2):97–104. [PubMed]
97. Hurley MV, Scott DL, Rees J, Newham DJ. Sensorimotor changes and functional
performance in patients with knee osteoarthritis. Annals of the Rheumatic Diseases.
1997;56(11):641–648. [PMC free article] [PubMed]
98. Pandya NK, Draganich LF, Mauer A, Piotrowski GA, Pottenger L, Pandya NK, et al.
Osteoarthritis of the knees increases the propensity to trip on an obstacle. Clinical
Orthopaedics & Related Research. 2005;(431):150–156. [PubMed]
99. Quick DC. Joint pain and weather. A critical review of the literature. Minnesota
Medicine. 1997;80(3):25–29. [Review] [24 refs]. [PubMed]
100. Wilder FV, Hall BJ, Barrett JP. Osteoarthritis pain and weather. Rheumatology.
2003;42(8):955–958. [PubMed]
101. Laborde JM, Dando WA, Powers MJ. Influence of weather on osteoarthritics. Social
Science & Medicine. 1986;23(6):549–554. [PubMed]
102. Strusberg I, Mendelberg RC, Serra HA, Strusberg AM. Influence of weather
conditions on rheumatic pain. Journal of Rheumatology. 2002;29(2):335–338. [PubMed]

The Role of Arthroscopy in Treating

Osteoarthritis of the Knee in the Older
Patient
Stephen M. Howell, MD

 Orthopedics
  September 2010 - Volume 33 · Issue 9

 Abstract
 Article

Abstract

Arthroscopy of the osteoarthritic knee is a common and costly practice with limited and
specific indications. The extent of osteoarthritis (OA) is determined by joint space
narrowing, which is best measured on a weight-bearing radiograph of the knee in 30° or
45° of flexion. The patient older than 40 years with a normal joint space should have a
magnetic resonance image taken to rule out focal cartilage wear and avascular necrosis
before undergoing arthroscopy. Randomized controlled trials of patients with joint space
narrowing have shown that outcomes after arthroscopic lavage or debridement are no
better than those after a sham procedure (placebo effect), and that arthroscopic surgery
provides no additional benefit to physical and medical therapy. The American Academy
of Orthopedic Surgeons guideline on the Treatment of Osteoarthritis of the Knee (2008)
recommended against performing arthroscopy with a primary diagnosis of OA of the
knee, with the caveat that partial meniscectomy or loose body removal is an option in
patients with OA that have primary mechanical signs and symptoms of a torn meniscus
and/or loose body. There is no evidence that removal of loose debris, cartilage flaps, torn
meniscal fragments, and inflammatory enzymes have any pain relief or functional benefit
in patients that have joint space narrowing on standing radiographs. Many patients with
joint space narrowing are older with multiple medical comorbidities. Consider the
complications and consequences when recommending arthroscopy to treat the painful
osteoarthritic knee without mechanical symptoms, as there is no proven clinical benefit.

This article presenting a case of a patient with a recent insidious onset of knee pain due to
osteoarthritis (OA) is used to illustrate the invaluable information gained from the use of
weight-bearing radiographs and magnetic resonance imaging (MRI) of the knee. The use
of standing radiographs in 30° or 45° of flexion to rule out joint space narrowing, and the
use of MRI in the knee without radiographic evidence of joint space narrowing to look
for wear of the articular cartilage and avascular necrosis before recommending
arthroscopy is stressed. Two level 1 studies and the American Academy of Orthopedic
Surgeons (AAOS) 2008 treatment guidelines are used to review the contraindications and
indications of arthroscopic treatment. Three relative indications for treating the painful
knee with mild OA and mechanical symptoms from a loose body, meniscus tear, and
anvil osteophyte with arthroscopy are discussed.

Common Presentation

A 60 year-old man who has struggled with his weight for years presented with 3 months
of medial knee pain that prevented him from walking his customary 2 miles a day and has
caused him to gain weight. The onset of his pain gradually increased without trauma. The
medial area of the knee became sorer the more he walked. He reported occasional night
pain that interfered with sleep. He had full motion, a trace effusion, but no mechanical
symptoms. His primary care physician treated him with nonsteroidal anti-inflammatory
medication, a trial of physical therapy, and a cortisone injection without lasting pain
relief. A weight-bearing radiograph of the knee in full extension showed marginal
osteophytes but no joint space narrowing, and the radiologist’s MRI report, which the
patient had read, identified a degenerative tear of the medial meniscus with cartilage
thinning on the medial tibia and femoral condyle (Figure 1). He is impatient, frustrated,
convinced that the torn meniscus is causing his pain, and that to resume walking and shed
his recent weight gain imposed by inactivity he needs arthroscopic surgery.

Figure 1: Weight-bearing radiograph of the

knee in full extension (A), MRI of the medial
hemijoint (B), and an intraoperative
photograph of the cartilage wear at time of
TKA (C). The weight-bearing radiograph in
full extension shows no medial joint space
 narrowing and underestimates the cartilage
wear shown in the MRI (arrow) and
intraoperative photograph (arrow). The
reading of the MRI indicated a degenerative
medial meniscal tear, however the patient’s
pain was more attributable to the lack of
articular cartilage on the femur and tibia
(arrow) than the incidental finding of the torn
meniscus. This patient should have had a
weight-bearing radiograph of the knee in 30°
to 45° of knee flexion to detect joint space
narrowing, which would have eliminated the
need for the MRI and any consideration of
arthroscopic treatment.

Should additional standing radiographs in flexion be obtained to determine the level of

arthritis before recommending arthroscopic treatment? How can the orthopedist use the
weight-bearing radiograph and MRI to counsel the patient as to the cause of the pain and
treatment alternatives? Is there evidence from Level 1 studies to support arthroscopic
treatment of his knee?

Use of Radiographs and MRI Before Recommending Arthroscopy

The patient’s age, extra weight, lack of trauma, and no mechanical symptoms suggest this
patient has a flare up of preexisting, unrecognized degenerative arthritis of the knee and
weight-bearing radiographs of both knees were indicated. Weight-bearing posteroanterior
radiographs of the knee in 30° or 45° of flexion should be ordered as the view of the knee
in flexion is more sensitive in detecting and showing more joint space narrowing than the
conventional anteroposterior radiograph in full extension that was described by Ahlbäck
in 1968 (Figure 2).1-3

Figure 2: Weight-bearing radiograph of a

 right knee showing the effect that imaging
the knee in full extension (left) and 45° of
flexion (right) has on detecting the amount
of joint space narrowing. The weight-
bearing view of the knee in 45° of flexion
shows no lateral joint space, while the view
in full extension shows 2 mm of joint space.
The best view for detecting joint space
narrowing is the weight-bearing 30° and
45° knee flexion view (right). Arthroscopic
treatment is rarely indicated when the
weight-bearing 30° and 45° knee flexion
view shows joint space narrowing.

Joint space narrowing of >2 mm on any weight-bearing radiographs was correlated at the
time of arthroscopy with ulceration involving the deep zones of the articular cartilage
(grade III) and exposure of subchondral bone (Grade IV).2 The orthopedist can counsel
the patient by showing the joint space narrowing on the weight-bearing radiograph of the
knee and explaining that there is a direct correlation between joint space narrowing and
the arthroscopic findings. With this explanation, the patient can better understand and
accept that the insidious pain is more attributable to preexisting underlying OA and not
the torn meniscus.

A patient older than 40 years with knee pain and weight-bearing radiographs in flexion
and extension that show no joint space narrowing should have an MRI of the knee to
rule-out cartilage wear and avascular necrosis before recommending arthroscopy (Figure
3). In the older patient, MRI often detects extensive areas of cartilage loss when the joint
space appears normal on standing radiographs. Showing the cartilage wear on the MRI to
the patient can help convince them their pain is more likely attributable to OA and that
arthroscopic removal of a degenerative meniscus tear is unlikely to provide benefit and
improve function. Further explanation that the prevalence of meniscus tears increases
with increasing age, and that asymptomatic meniscal tears on MRI of the knee are
common in the general population with no knee pain, aching, or stiffness may be needed.4

Figure 3: MRI of the medial hemijoint of a

 knee showing a degenerative meniscal tear,
mild cartilage loss, and subchondral fracture
in the proximal tibia due to avascular
necrosis. The patient read the radiologist’s
description of the study and falsely
concluded that the meniscal tear caused his
symptoms and insisted on arthroscopic
treatment. The patient was convinced after
seeing the subchondral fracture and the mild
cartilage loss that arthroscopic treatment
would not be helpful. The MRI can change
treatment recommendations when weight-
bearing radiographs do not show joint space
narrowing.

Contraindications for Treating the OA Knee With Arthroscopy

Many patients report symptomatic relief after undergoing arthroscopy of the knee for OA,
however it has been unclear how the procedure achieves this result.5 A randomized
clinical trial in a single center by a single surgeon in predominantly male patients with
moderate and severe joint space narrowing (Kellgren-Lawrence grade 3 and 4)6 showed
that outcomes after arthroscopic lavage or arthroscopic debridement were no better than
those after a sham procedure (placebo effect).7 A randomized clinical trial in a single
center by multiple surgeons in a population consisting of 60% women with mild to severe
joint space narrowing (Kellgren-Lawrence grade 2 to 4) showed that arthroscopic surgery
for OA of the knee provided no additional benefit to physical therapy (1 session per week
for 12 weeks followed by an unsupervised program at home), patient education, and the
stepwise use of acetaminophen, nonsteroidal anti-inflammatory drugs, glucosamine, and
the injection of hyaluronic acid.5,8 Accordingly, the American Academy recommended
against performing arthroscopy with debridement or lavage in patients with primary
diagnosis of symptomatic OA of the knee (Guideline 18); however, they recommended
considering partial meniscectomy or loose body removal in patients with symptomatic
OA of the knee who also have primary signs and symptoms of a torn meniscus and/or a
loose body (Guideline 19).9

Three Indications for Treating the OA Knee With Arthroscopy

One indication for treating the knee with mild to severe OA with arthroscopy is the
complaint of mechanical symptoms from a loose body and (Figure 4). For the loose body
to be mobile and cause locking, it should reside anterior to the knee in the suprapatellar
pouch on the radiograph. A posterior loose body typically is not mobile and does not
cause locking because it is trapped inside the walls of a Baker’s cyst. A second indication
is arthroscopic removal of a meniscal tear when the presenting symptoms are mechanical
with pain localized on the joint line in the knee with mild joint space narrowing
(Kellegren-Lawrence grade 1). A meniscal tear is rarely the primary cause of pain in the
knee with radiographic moderate to severe OA (Kellegren-lawrence grade 3 and 4). The
third indication is arthroscopic excision of an anterior anvil osteophyte to improve
extension in the knee with mild OA and a flexion contracture (Figure 5).10

Figure 4: Lateral radiographs of 2 knees showing the

typical location of symptomatic (left) and asymptomatic
(right) loose bodies in the osteoarthritic knee. Symptomatic
loose bodies are anterior to the knee in the suprapatellar
pouch and are mobile. Asymptomatic loose bodies are
posterior to the knee and because they are trapped in a
Baker’s cyst they are not mobile and do not cause
mechanical symptoms of locking.

Figure 5: Lateral radiograph shows

an anvil osteophyte (outlined by
dots) in a knee with a flexion
 contracture and mild osteoarthritis.
Arthroscopic excision of the anvil
osteophyte can remove the
mechanical block between the anvil
osteophyte and the intercondylar
notch and restore extension.

Conclusion

A patient should not be treated with arthroscopy when the weight-bearing radiographs in
either 0° and 45° of knee flexion show joint space narrowing, the MRI shows substantial
cartilage wear indicating OA, and there are no mechanical symptoms of a loose body,
meniscal tear, or an extension loss from an anvil osteophyte. Counsel the patient that the
prevalence of coexisting meniscal tears and OA in middle-aged and elderly patients is
high4,8 and that arthroscopic debridement of the osteoarthritic knee is no more effective
than sham surgery and physical and medical therapy. 5,7

References

1. Davies AP, Calder DA, Marshall T, Glasgow MM. Plain radiography in the
degenerate knee. A case for change. J Bone Joint Surg Br. 1999; 81(4):632-635.
2. Rosenberg TD, Paulos LE, Parker RD, Coward DB, Scott SM. The forty-five-
degree posteroanterior flexion weight-bearing radiograph of the knee. J Bone
Joint Surg Am. 1988; 70(10):1479-1483.
3. Ahlback S. Osteoarthrosis of the knee. A radiographic investigation. Acta Radiol
Diagn (Stockh). 1968; (Suppl 277):7-72.
4. Englund M, Guermazi A, Gale D, et al. Incidental meniscal findings on knee MRI
in middle-aged and elderly persons. N Engl J Med. 2008; 359(11):1108-1115.
5. Kirkley A, Birmingham TB, Litchfield RB, et al. A randomized trial of
arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2008;
359(11):1097-1107.
6. Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann
Rheum Dis. 1957; 16(4):494-502.
7. Moseley JB, O’Malley K, Petersen NJ, et al. A controlled trial of arthroscopic
surgery for osteoarthritis of the knee. N Engl J Med. 2002; 347(2):81-88.
8. Marx RG. Arthroscopic surgery for osteoarthritis of the knee? N Engl J Med.
2008; 359(11):1169-1170.
9. AAOS Guidelines. Treatment of osteoarthritis of the knee (non-arthroplasty).
http://www.aaos.org/research/guidelines/guide.asp. Accessed June 24, 2009.
10. Lakdawala A, Ireland J. The ‘anvil’ osteophyte-a primary cause of fixed flexion of
the knee? Knee. 2005; 12(3):191-193.