Research paper- knee osteoarthritis

Outline: Discuss the typical clinical presentation as it relates to the diagnosis. You are also to include possible treatment interventions as it relates to therapeutic exercise. Recommendation for the management of the condition.

Introduction:

· Describe the pathophysiology of the diagnosis and the expected clinical presentation anticipated. If it varies, then describe common variations

· Discuss etiology and demographics related to the diagnosis. (is the diagnosis is more common in women or men, what age group, etc)

Body of paper:

· Describe selected therapeutic activities/exercises to address deficits and discuss the rationale

· Discuss how a person with the assigned diagnosis should progress through the following phases and discuss the clinical presentation as it relates to each phase of rehabilitation to include specific musculature involved:

· Maximum protection phase

· Controlled motion or moderate protection phase

· Return to function phase

Conclusion

Reference page: 5 reference total, 3 research studies

APA style, 12 font, Times New Roman, and doubled spaced

At least six pages long, not including title page, reference page.

June 1, 2011 ◆ Volume 83, Number 11 www.aafp.org/afp American Family Physician  1287

Treatment of Knee Osteoarthritis
ERIKA RINGDAHL, MD, and SANDESH PANDIT, MD
University of Missouri School of Medicine, Columbia, Missouri

O
steoarthritis is a degenera-
tive joint disease occurring
primarily in older adults. It is
characterized by erosion of the

articular cartilage, hypertrophy of bone at
the margins (i.e., osteophytes), and sub-
chondral sclerosis.1 Arthritis is the leading
cause of disability in the United States,2 and
osteoarthritis is the most common condi-
tion affecting synovial joints.3 Despite its

widespread prevalence, however, the precise
etiology, pathogenesis, and progression of
osteoarthritis are unknown. Several factors
may make a person vulnerable to the disease
(Table 1).

Osteoarthritis affects 33.6 percent of per-
sons older than 65 years.4 About 80 percent
of patients with knee osteoarthritis have
some limitation of movement, and 25 per-
cent cannot perform major activities of daily
living.4 Approximately 11 percent of adults
with knee osteoarthritis need help with per-
sonal care.4

Diagnosis of Osteoarthritis
The most common presenting symptom in
persons with knee osteoarthritis is pain that
is worse with use and better with rest. Other
presenting signs and symptoms include stiff-
ness that generally improves after 30 minutes
of activity (inactivity gelling), crepitus, swell-
ing, and limp. In advanced cases, patients
may present with instability symptoms or
genu valgum (knock knee) or varum (bow-
leg). Varus deformity is more common than

Knee osteoarthritis is a common disabling condition that affects
more than one-third of persons older than 65 years. Exercise, weight
loss, physical therapy, intra-articular corticosteroid injections, and
the use of nonsteroidal anti-inflammatory drugs and braces or heel
wedges decrease pain and improve function. Acetaminophen, glu-
cosamine, ginger, S-adenosylmethionine (SAM-e), capsaicin cream,
topical nonsteroidal anti-inflammatory drugs, acupuncture, and tai
chi may offer some benefit. Tramadol has a poor trade-off between
risks and benefits and is not routinely recommended. Opioids are
being used more often in patients with moderate to severe pain or
diminished quality of life, but patients receiving these drugs must
be carefully selected and monitored because of the inherent adverse
effects. Intra-articular corticosteroid injections are effective, but
evidence for injection of hyaluronic acid is mixed. Arthroscopic sur-
gery has been shown to have no benefit in knee osteoarthritis. Total
joint arthroplasty of the knee should be considered when conserva-
tive symptomatic management is ineffective. (Am Fam Physician.
2011;83(11):1287-1292. Copyright © 2011 American Academy of
Family Physicians.)

▲

Patient information:
A handout on knee osteo-
arthritis, written by the
authors of this article, is
provided on page 1294.

IL
LU

S
T

R
A

T
IO

N
B

Y
T

O
D

D
B

U
C

K

Table 1. Common Risk Factors  
for 

Knee Osteoarthritis

Female sex

Inflammatory joint disease (e.g., infection, gout,
rheumatoid arthritis)

No history of osteoporosis

Obesity (strongest modifiable risk factor)

Occupation requiring repetitive knee bending

Older age

Previous knee injury (e.g., torn meniscus, intra-
articular mechanical damage)

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Knee Osteoarthritis

1288  American Family Physician www.aafp.org/afp Volume 83, Number 11 ◆ June 1, 2011

valgus deformity because the medial com-
partment of the knee is more often involved.

The differential diagnosis of chronic knee
pain is given in Table 2. The criteria for
diagnosing knee osteoarthritis are based on
the presence of knee pain plus at least three
of the six clinical characteristics listed in
Table 3.5,6 The addition of laboratory and
radiographic criteria enchances the diag-
nostic accuracy; however, these tests are not
necessary for all patients. In most patients,
the history, physical examination, and radi-
ography are all that is needed.

Treatment
PHYSICAL MODALITIES AND EXERCISE

Physical modalities for the treatment of knee
pain in patients with osteoarthritis include
physical therapy, exercise, weight loss, and
the use of braces or heel wedges. A review of
physical therapy interventions for patients
with knee osteoarthritis concluded that

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation
Evidence
rating References

Water- or land-based exercise, aerobic walking, quadriceps
strengthening, resistance exercise, and tai chi reduce pain and disability
from knee osteoarthritis.

A 7-13

Glucosamine supplementation may provide some benefit for persons
with knee osteoarthritis, especially in those with moderate to severe
pain. However, the evidence for this benefit is mixed.

B 15

Chondroitin supplementation does not decrease pain in persons with
knee osteoarthritis.

B 15

Acupuncture may provide some benefit in persons with knee
osteoarthritis; however, the evidence is weak.

B 16, 17

S-adenosylmethionine (SAM-e) is as effective as nonsteroidal anti-
inflammatory drugs in reducing pain and disability from knee osteoarthritis.

B 18

Nonsteroidal anti-inflammatory drugs and acetaminophen improve pain
in persons with knee osteoarthritis.

A 25, 28

Older patients with moderate to severe pain from knee osteoarthritis may
experience modest benefit with tramadol (Ultram); however, its use is
limited by adverse effects.

B 29

Intra-articular corticosteroid injections provide short-term benefit with
few adverse effects in the treatment of knee osteoarthritis.

A 32, 33

Evidence is mixed for the effectiveness of hyaluronic acid injections for
the treatment of knee osteoarthritis.

B 34

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evi-
dence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information
about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml.

Table 2. Differential Diagnosis  
of Knee Pain

Conditions involving soft tissue of knee

Bursitis

Iliotibial band syndrome

Ligamentous instability (medial and lateral
collateral ligaments)

Meniscal pathology

Other forms of arthritis

Gout and pseudogout

Rheumatoid arthritis

Septic arthritis

Referred pain

Neuropathy

Radiculopathy

Other

Avascular necrosis

Patellofemoral pain syndrome

Tumor

Knee Osteoarthritis

June 1, 2011 ◆ Volume 83, Number 11 www.aafp.org/afp American Family Physician  1289

exercise and weight loss reduce pain and
improve physical function.7 Exercise should
be prescribed as a treatment for knee osteo-
arthritis. High- and low-intensity aerobic
exercises are equally effective in improving
functional status, gait, pain, and aerobic
capacity in persons with knee osteoarthri-
tis8; water-based and land-based exercises
reduce knee pain and physical disability9,10;
and aerobic walking, quadriceps strengthen-
ing, and resistance exercise reduce pain and
disability.11,12 A small randomized controlled
trial (RCT) showed that performing tai chi
three times per week for 12 weeks decreased
pain and improved physical functioning in
older women with knee osteoarthritis.13 Any
activity that worsens knee pain should be
discontinued.

The use of braces and heel wedges may
also be effective for treatment of knee osteo-
arthritis. There is some evidence that the
use of a lateral heel wedge decreases the use
of nonsteroidal anti-inflammatory drugs
(NSAIDs).14 Similar evidence suggests that
a brace and lateral wedge insole may have
a small beneficial effect.14 Braces and heel
wedges can be customized and purchased at
stores specializing in orthotics.

COMPLEMENTARY AND ALTERNATIVE MEDICINE

Many complementary and alternative medi-
cine treatments have been used to treat knee
osteoarthritis, with variable success. Glucos-
amine and chondroitin supplements have
been marketed since the 1990s as disease-
modifying options. A double-blind RCT
showed little benefit from the use of glu-
cosamine combined with chondroitin in
participants with mild knee osteoarthri-
tis.15 However, a greater benefit was noted in
persons with moderate to severe pain. Glu-
cosamine is safe, but the benefit is variable.
Chondroitin does not decrease pain from
osteoarthritis of the knee or hip.15

The benefit of acupuncture is not clear.
A meta-analysis did not demonstrate any
clinically relevant improvement in pain or
function scores with acupuncture compared
with sham acupuncture.16 However, in the
short term (six weeks) and in the long term
(six months), patients who received either

acupuncture or sham acupuncture felt better
than those who received usual care. Another
study showed that six months of treat-
ment with traditional Chinese acupuncture
decreased pain scores and increased func-
tionality an average of 40 percent compared
with sham acupuncture or no treatment.17

Supplementation with S-adenosylmethi-
onine (SAM-e), ginger (Zingiber officinale),
or turmeric (Curcuma longa) has also been
promoted as treatment for osteoarthritis. A
meta-analysis of RCTs found that SAM-e is
as effective as NSAIDs in reducing pain and
disability, and has a better safety profile.18
Ginger may provide some clinical benefit in
patients with knee osteoarthritis; patients
who took 255 mg of ginger extract twice
daily had a reduction in pain (63 percent

Table 3. Diagnosis of Knee Osteoarthritis

Clinical criteria

Age older than 50 years

Bony enlargement

Bony tenderness

Crepitus

No palpable warmth

Stiffness for less than 30 minutes

Laboratory criteria

Erythrocyte sedimentation rate less than 40 mm per hour

Rheumatoid factor less than 1:40

Synovial fluid analysis: clear, viscous, white blood cell count less than
2,000 per µL (2.00 x 109 per L)

Radiographic criteria

Presence of osteophytes

Diagnostic accuracy

Criteria Sensitivity (%) Specificity (%) LR+ LR–

Knee pain plus at least
three clinical criteria

95 69 3.1 0.07

Knee pain plus at
least five clinical or
laboratory criteria

92 75 3.7 0.11

Knee pain plus at
least five clinical or
laboratory criteria, plus
osteophytes present

91 86 6.5 0.10

LR+ = positive likelihood ratio; LR– = negative likelihood ratio.

Information from references 5 and 6.

Knee Osteoarthritis

1290  American Family Physician www.aafp.org/afp Volume 83, Number 11 ◆ June 1, 2011

compared with 50 percent in the placebo
group).19 Turmeric historically has been used
to treat arthritis pain, but no clinical trials
have shown it to be effective.20

PHARMACOLOGIC TREATMENT

Pharmacologic treatments can be catego-
rized as topical, oral, or intra-articular. The
use of topical therapies avoids many of the
adverse effects associated with systemic med-

ications. A review of placebo-
controlled trials of capsaicin
cream 0.025% (Zostrix) con-
cluded that it was statistically
more effective than placebo,
but less effective than topi-
cal NSAIDs.21 A meta-analysis
of RCTs compared topical

NSAIDs with placebo or oral NSAIDs in
patients with knee osteoarthritis.22 Topical
NSAIDs were superior to placebo in reliev-
ing pain, but only for the first two weeks of
treatment. Topical NSAIDs were less effec-
tive than oral NSAIDs, even in the first week
of treatment.

Many oral medications are available for
managing pain from knee osteoarthritis.
Acetaminophen is the preferred drug in
guidelines from the American College of
Rheumatology.23 It is more effective than
placebo in the treatment of osteoarthri-
tis pain.24 Liver toxicity is extremely rare,
although caution should be used in patients
who consume alcohol daily. Patients taking
3 to 4 g of acetaminophen per day should
have regular monitoring of kidney and
liver function. NSAIDs are slightly supe-
rior to acetaminophen for improving knee
and hip pain in patients with osteoarthritis,
especially in those with moderate to severe
pain.25 There is no difference in clinical
effectiveness among NSAIDs.25

Cyclooxygenase-2 (COX-2) inhibitors may
have a role in the treatment of osteoarthritis.
Celecoxib (Celebrex) is the only prototype
COX-2 inhibitor available because rofecoxib
and valdecoxib have been withdrawn from
the market because of adverse cardiovascular
effects. However, celecoxib is also associated
with an increased incidence of myocar-
dial infarction and stroke.26 A systematic

review showed that although the use of cele-
coxib results in similar symptom control as
other NSAIDs and does not reduce the risk
of serious adverse gastrointestinal effects,
patients may be less likely to stop taking cele-
coxib because of gastrointestinal effects.27,28
Although there is no increased risk of adverse
effects with the use of COX-2 inhibitors for
treatment of osteoarthritis compared with
other NSAIDs, there also may not be much
benefit.

Opioids also may have a beneficial role
in the treatment of knee osteoarthritis.
Guidelines from the American College of
Rheumatology support the use of opioid
therapy when other treatments have been
ineffective or are inappropriate.23 Tramadol
(Ultram), with or without acetaminophen,
decreases pain intensity, relieves symp-
toms, and improves function.29 Tramadol
increases the risk of seizure, especially in
patients who drink alcohol. A recent guide-
line from the American Geriatrics Society
recommends that all older patients with
moderate to severe pain or diminished qual-
ity of life be considered for opioid therapy.30
The risks of NSAID use in older patients,
including increased cardiovascular risk and
gastrointestinal toxicity, may exceed the
potential for addiction in these patients.
However, propoxyphene, which was taken
off the market in November 2010, should be
avoided because it is no more effective than
acetaminophen and is associated with more
adverse effects.31

INTRA-ARTICULAR INJECTIONS

Intra-articular corticosteroid injections may
provide short-term symptomatic relief in
patients with knee osteoarthritis, with low
risk of adverse effects. A systematic review
of 28 clinical trials found a significant short-
term reduction in pain and improvement in
patient self-assessment with intra-articular
corticosteroid injection compared with pla-
cebo injection32; however, good evidence
of long-term benefit is lacking. The precise
mechanism of action is unknown, but cor-
ticosteroids are presumed to inhibit accu-
mulation of inflammatory cell lines, reduce
prostaglandin synthesis, inhibit leukocyte

Topical nonsteroidal anti-
inflammatory drugs are 
effective for short-term 
pain relief in persons with 
knee osteoarthritis.

Knee Osteoarthritis

June 1, 2011 ◆ Volume 83, Number 11 www.aafp.org/afp American Family Physician  1291

secretion from synovial cells, and decrease
interleukin secretion by the synovium. A
typical dose for knee injections is 40 mg of
triamcinolone acetonide (Kenalog), with a
number needed to treat of two or three.33

Intra-articular hyaluronic acid injections
(e.g., Synvisc, Euflexxa) for osteoarthritis are
minimally effective. Despite being promoted
as potential disease-modifying agents, no
study has demonstrated that these drugs
alter the disease course. Synovial fluid is an
ultrafiltrate of plasma modified by the addi-
tion of hyaluronic acid, which is produced
by the synovium. In persons with osteo-
arthritis, the hyaluronic acid is decreased
and compromised. Exogenous supplemen-
tation of intra-articular hyaluronic acid is
thought to support and restore the elastovi-
scous properties of synovial fluid. However,
a meta-analysis showed that studies demon-
strating benefit from intra-articular hyal-
uronic acid injections were poorly designed
or industry sponsored, whereas other stud-
ies demonstrated no clinically significant
improvement in function.34

SURGERY

Arthroscopic surgery is not an appropri-
ate treatment for knee osteoarthritis unless
there is evidence of loose bodies or mechani-
cal symptoms such as locking, giving way,
or catching. Two well-designed RCTs of
arthroscopic surgery for treatment of knee
osteoarthritis showed no benefit.35,36

Total knee replacement should be consid-
ered as a last resort. According to the Ameri-
can Academy of Orthopedic Surgeons, the
main indication for total knee arthroplasty
is relief of pain associated with knee osteo-
arthritis if nonsurgical treatment has been
ineffective. The complication rate of total
knee replacement is 5.4 percent of patients
and 7.6 percent of knees.37

Data Sources: A Medline search was performed, which
included meta-analyses, randomized controlled trials, clini-
cal trials, and systematic reviews. Also searched were the
Cochrane Database of Systematic Reviews, UpToDate, the
Centers for Disease Control and Prevention, and DynaMed.
Search period: November 18, 2009, to September 1, 2010.

The authors thank Susan Meadows for assistance with
the literature search.

The Authors

ERIKA RINGDAHL, MD, is a clinical professor in the Depart-
ment of Family and Community Medicine at the University
of Missouri School of Medicine, Columbia.

SANDESH PANDIT, MD, is a sports medicine fellow at Saint
Vincent Health System in Erie, Pa. At the time this article
was written, he was a resident in the Department of Fam-
ily and Community Medicine at the University of Missouri
School of Medicine.

Address correspondence to Erika Ringdahl, MD, Uni-
versity of Missouri School of Medicine, MA303, Medical
Sciences Building, Columbia, MO 65212 (e-mail: ring-
dahle@health.missouri.edu). Reprints are not available
from the authors.

Author disclosure: Nothing to disclose.

REFERENCES

1. Di Cesare P, Abramson S, Samuels J. Pathogenesis of
osteoarthritis. In: Firestein GS, Kelley WN, eds. Kelley’s
Textbook of Rheumatology. 8th ed. Philadelphia, Pa.:
Saunders Elsevier; 2009:1525-1540.

2. Centers for Disease Control and Prevention. Prevalence
and most common causes of disability among adults—
United States, 2005. MMWR Morb Mortal Wkly Rep.
2009;58(16):421-426.

3. Lopez AD, Murray CC. The global burden of disease,
1990-2020. Nat Med. 1998;4(11):1241-1243.

4. Centers for Disease Control and Prevention. Osteoarthritis.
http://www.cdc.gov/arthritis/basics/osteoarthritis.htm.
Accessed March 1, 2010.

5. Altman R, Asch E, Bloch D, et al.; Diagnostic and Thera-
peutic Criteria Committee of the American Rheumatism
Association. Development of criteria for the classifi-
cation and reporting of osteoarthritis. Classification
of osteoarthritis of the knee. Arthritis Rheum. 1986;
29(8):1039-1049.

6. Wu CW, Morrell MR, Heinze E, et al. Validation of
American College of Rheumatology classification crite-
ria for knee osteoarthritis using arthroscopically defined
cartilage damage scores. Semin Arthritis Rheum. 2005;
35(3):197-201.

7. Jamtvedt G, Dahm KT, Christie A, et al. Physical therapy
interventions for patients with osteoarthritis of the
knee: an overview of systematic reviews. Phys Ther.
2008;88(1):123-136.

8. Fransen M, McConnell S. Exercise for osteoarthritis
of the knee. Cochrane Database Syst Rev. 2008;(4):
CD004376.

9. Fransen M, McConnell S. Land-based exercise for osteo-
arthritis of the knee: a metaanalysis of randomized con-
trolled trials. J Rheumatol. 2009;36(6):1109-1117.

10. Silva LE, Valim V, Pessanha AP, et al. Hydrotherapy
versus conventional land-based exercise for the man-
agement of patients with osteoarthritis of the knee: a
randomized clinical trial. Phys Ther. 2008;88(1):12-21.

11. Roddy E, Zhang W, Doherty M. Aerobic walking or
strengthening exercise for osteoarthritis of the knee?
A systematic review. Ann Rheum Dis. 2005;64(4):
544-548.

Knee Osteoarthritis

1292  American Family Physician www.aafp.org/afp Volume 83, Number 11 ◆ June 1, 2011

12. Ettinger WH Jr, Burns R, Messier SP, et al. A randomized
controlled trial comparing aerobic exercise and resis-
tance exercise with a health education program in older
adults with knee osteoarthritis. The Fitness Arthritis and
Seniors Trial (FAST). JAMA. 1997;277(1):25-31.

13. Song R, Lee EO, Lam P, Bae SC. Effects of tai chi exer-
cise on pain, balance, muscle strength, and perceived
difficulties in physical functioning in older women with
osteoarthritis: a randomized clinical trial. J Rheumatol.
2003;30 (9):2039-2044.

14. Brouwer RW, Jakma TS, Verhagen AP, Verhaar JA,
Bierma-Zeinstra SM. Braces and orthoses for treating
osteoarthritis of the knee. Cochrane Database Syst Rev.
2005;(1):CD004020.

15. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chon-
droitin sulfate, and the two in combination for pain-
ful knee osteoarthritis. N Engl J Med. 2006;354(8):
795-808.

16. Manheimer E, Linde K, Lao L, Bouter LM, Berman BM.
Meta-analysis: acupuncture for osteoarthritis of the
knee. Ann Intern Med. 2007;146(12):868-877.

17. Berman BM, Lao L, Langenberg P, Lee WL, Gilpin AM,
Hochberg MC. Effectiveness of acupuncture as adjunc-
tive therapy in osteoarthritis of the knee: a randomized,
controlled trial. Ann Intern Med. 2004;141(12):901-910.

18. Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BM.
Safety and efficacy of S-adenosylmethionine (SAMe)
for osteoarthritis. J Fam Pract. 2002;51(5):425-430.

19. Altman RD, Marcussen KC. Effects of a ginger extract
on knee pain in patients with osteoarthritis. Arthritis
Rheum. 2001;44(11):2531-2538.

20. Medline Plus. Turmeric. http://www.nlm.nih.gov/
medlineplus/druginfo/natural/662.html. Accessed
August 20, 2010.

21. Mason L, Moore RA, Derry S, Edwards JE, McQuay HJ.
Systematic review of topical capsaicin for the treatment
of chronic pain. BMJ. 2004;328(7446):991.

22. Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical
non-steroidal anti-inflammatory drugs in the treatment
of osteoarthritis: meta-analysis of randomised con-
trolled trials. BMJ. 2004;329(7461):324.

23. American College of Rheumatology Subcommittee
on Osteoarthritis Guidelines. Recommendations for
the medical management of osteoarthritis of the hip
and knee: 2000 update. Arthritis Rheum. 2000;43(9):
1905-1915.

24. Towheed TE, Maxwell L, Judd MG, Catton M, Hoch-
berg MC, Wells G. Acetaminophen for osteoarthritis.
Cochrane Database Syst Rev. 2006;(1):CD004257.

25. Geba GP, Weaver AL, Polis AB, Dixon ME, Schnitzer TJ;
Vioxx, Acetaminophen, Celecoxib Trial (VACT) Group.

Efficacy of rofecoxib, celecoxib, and acetaminophen in
osteoarthritis of the knee: a randomized trial [published
correction appears in JAMA. 2002;287(8):989]. JAMA.
2002;287(1):64-71.

26. White WB, West CR, Borer JS, et al. Risk of cardiovas-
cular events in patients receiving celecoxib: a meta-
analysis of randomized clinical trials. Am J Cardiol. 2007;
99(1):91-98.

27. Silverstein FE, Faich G, Goldstein JL, et al. Gastroin-
testinal toxicity with celecoxib vs nonsteroidal anti-
inflammatory drugs for osteoarthritis and rheumatoid
arthritis: the CLASS study: a randomized controlled
trial. JAMA. 2000;284(10):1247-1255.

28. Deeks JJ, Smith LA, Bradley MD. Efficacy, tolerability,
and upper gastrointestinal safety of celecoxib for treat-
ment of osteoarthritis and rheumatoid arthritis: sys-
tematic review of randomised controlled trials. BMJ.
2002;325(7365):619.

29. Cepeda MS, Camargo F, Zea C, Valencia L. Tramadol
for osteoarthritis. Cochrane Database Syst Rev. 2006;
3:CD005522.

30. American Geriatrics Society Panel on Pharmacological
Management of Persistent Pain in Older Persons. Phar-
macological management of persistent pain in older
persons. J Am Geriatr Soc. 2009;57(8):1331-1346.

31. Li Wan Po A, Zhang WY. Systematic overview of co-
proxamol to assess analgesic effects of addition of
dextropropoxyphene to paracetamol [published cor-
rections appear in BMJ. 1998;316(7125):116, and BMJ.
1998;316(7132):656]. BMJ. 1997;315(7122):1565-1571.

32. Bellamy N, Campbell J, Robinson V, Gee T, Bourne R,
Wells G. Intraarticular corticosteroid for treatment of
osteoarthritis of the knee. Cochrane Database Syst Rev.
2006;(2):CD005328.

33. Arroll B, Goodyear-Smith F. Corticosteroid injections for
osteoarthritis of the knee: meta-analysis. BMJ. 2004;
328(7444):869.

34. Arrich J, Piribauer F, Mad P, Schmid D, Klaushofer K,
Müllner M. Intra-articular hyaluronic acid for the treat-
ment of osteoarthritis of the knee: systematic review
and meta-analysis. CMAJ. 2005;172(8):1039-1043.

35. 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.

36. Kirkley A, Birmingham TB, Litchfield RB, et al. A ran-
domized trial of arthroscopic surgery for osteoarthritis
of the knee [published correction appears in N Engl
J Med. 2009;361(20):2004]. N Engl J Med. 2008;
359(11):1097-1107.

37. Kane RL, Saleh KJ, Wilt TJ, et al. Total knee replacement.
Evid Rep Technol Assess (Summ). 2003;(86):1-8.

Progressive Resistance Training
Improves Overall Physical Activity
Levels in Patients With Early
Osteoarthritis of the Knee:
A Randomized Controlled Trial
Joshua N. Farr, Scott B. Going, Patrick E. McKnight, Shelley Kasle, Ellen C. Cussler,
Michelle Cornett

Background. Prescription of resistance training (RT) exercises is an essential
aspect of management for knee osteoarthritis (OA). However, whether patients with
knee OA who are randomly assigned to receive RT simply substitute RT for other
modes of physical activity remains unclear.

Objective. The aim of this study was to determine the effect of a structured RT
intervention on overall levels of moderate- and vigorous-intensity physical activity
(MVPA) in patients with early-onset knee OA. The study compared patients with
early-onset OA who participated in an RT program, those who participated in a
self-management (SM) program, and those who participated in both RT and SM.
Because participants randomly assigned to receive the RT intervention may simply
switch activity modes, resulting in little net effect, we assessed total MVPA in addition
to tracking changes in strength (force-generating capacity).

Design and Intervention. This study was a randomized controlled trial com-
paring the effectiveness of SM alone, RT alone, and combined RT�SM on MVPA in
patients with early OA of the knee.

Setting. The study was conducted on a university campus, with patient recruit-
ment from the local community.

Participants. The participants in this study were 171 patients (74% women, 26%
men) with knee OA. They had a mean age of 55.1 (SD�7.1) years, a mean body mass
index of 27.6 (SD�4.2) kg/m2, and radiographic status of grade II OA (and no higher)
in at least one knee, as defined by the Kellgren and Lawrence classification. They
wore an accelerometer while awake (X�14.2 [SD�2.2] hours) for 5 to 7 contiguous
days (X�6.8 [SD�0.5] days) at baseline and at 3 and 9 months of intervention.

Results. The participants engaged in MVPA a mean of 26.2 (SD�19.3) minutes per
day at baseline. Both groups significantly increased their MVPA from baseline to 3
months (RT group by 18% [effect size (d)�0.26]; SM group by 22% [effect size
(d)�0.25]), but only the RT group sustained those changes at 9 months (RT group
maintained a 10% increase [effect size (d)�0.15]; SM group maintained a 2% increase
[effect size (d)�0.03]). A significant group � time interaction for MVPA indicated
that the RT group maintained higher MVPA levels than the SM group.

Limitations. Lack of direct measures of energy expenditure and physical function
was a limitation of the study.

Conclusions. Patients with early-onset OA of the knee can engage in an RT
program without sacrificing their overall MVPA levels. These results support the
value of RT for management of knee OA.

J.N. Farr, MS, is Research Assistant,
Department of Physiological Sci-
ences, University of Arizona, 1713
E University Blvd #93, Tucson, AZ
85721 (USA). Address all corre-
spondence to Mr Farr at: jfarr@
email.arizona.edu.

S.B. Going, PhD, is Professor, De-
partment of Nutritional Sciences,
University of Arizona.

P.E. McKnight, PhD, is Assistant
Professor of Psychology, Depart-
ment of Psychology, George Ma-
son University, Fairfax, Virginia.

S. Kasle, PhD, is Research Assistant
Professor, Arizona Arthritis Center,
College of Medicine, University of
Arizona.

E.C. Cussler, MS, is Data Manager,
Department of Physiological Sci-
ences, University of Arizona.

M. Cornett, RN, is Senior Research
Nurse, Arizona Arthritis Center,
College of Medicine, University of
Arizona.

[Farr JN, Going SB, McKnight PE,
et al. Progressive resistance train-
ing improves overall physical ac-
tivity levels in patients with early
osteoarthritis of the knee: a ran-
domized controlled trial. Phys
Ther. 2010;90:356 –366.]

© 2010 American Physical Therapy
Association

Research Report

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The primary goals of knee osteo-arthritis (OA) treatment are toreduce pain and improve func-
tion and quality of life. Declining en-
thusiasm for cyclo-oxygenase 2 in-
hibitors for knee OA pain relief and
unsuccessful clinical trials of disease-
modifying OA drugs have contrib-
uted to increased interest in non-
pharmacologic treatments for OA.1

Resistance training (RT) exercise
programs and educational self-
management (SM) programs are 2
mainstays of nonpharmacologic
treatment.

Physical activity (PA) refers to any
bodily movement that results in en-
ergy expenditure. Physical activity is
an essential recommendation in-
cluded in all guidelines for manage-
ment of knee OA.2– 4 Moreover, PA is
recommended by the US Centers for
Disease Control and Prevention
(CDC) and the American College of
Sports Medicine (ACSM) for general
health to reduce risks of obesity-
linked health problems, including di-
abetes and cardiovascular disease,5,6

which often coexist with knee OA.
Work group recommendations from
the 2002 Exercise and Physical Ac-
tivity Conference (EPAC)7 advise pa-
tients with knee OA to accumulate
30 minutes of at least moderate-
intensity (�3 metabolic equivalents
[METs]*) PA on at least 3 days of the
week. The expert EPAC panel con-
cluded that promotion of PA in
adults with arthritis should empha-
size aerobic moderate- and vigorous-
intensity physical activity (MVPA,
�3 METs) and muscle strengthening
resistance exercise. In a more recent
statement, an expert consensus
panel provided evidence-based rec-
ommendations for practical delivery
of exercise therapy for patients with
knee OA, stating that “both general
(aerobic fitness training) and local
(strengthening) exercises are essen-

tial, core aspects of management for
every patient with knee OA.”8(p69)

In recent years, it has become clear
that RT can have a positive effect on
resting energy expenditure (REE), to-
tal free-living energy expenditure
(TEE), and activity-related energy ex-
penditure (AEE). Withers et al9 com-
pared REE, TEE, and AEE of chroni-
cally active women who engaged in
RT and chronically inactive women,
aged 49 to 70 years. They reported
that the chronically active women
had increased REE, TEE, and AEE
compared with the chronically inac-
tive women. Hunter et al10 addressed
this concern in elderly men and
women who were healthy, aged 61
to 77 years. They found increases in
REE, TEE, and AEE in response to 26
weeks of RT and showed that the
TEE increase remained significant
even after adjustment for the energy
expenditure of the RT. These find-
ings suggest that RT has value in in-
creasing energy expenditure and
lipid oxidation rates in older adults.

A potential concern when structured
RT programs are prescribed is that
participants may simply switch activ-
ity modes, resulting in a decrease in
aerobic MVPA. For example, Goran
and Poehlman11 and Meijer et al12

both observed a compensatory de-
crease in free-living PA levels of older
adults after engaging in RT pro-
grams. However, we found no stud-
ies that have addressed this concern
in a patient population such as pa-
tients with early OA of the knee. Al-
though controlling mode is desirable
for study purposes, in clinical and
public health settings, replacement
of one mode with another may de-
feat efforts to increase overall MVPA.
In contexts such as the present
study, participants randomly as-
signed to receive RT might engage in
less overall MVPA, substituting RT
for other modes of MVPA. Alterna-
tively, if participants randomly as-
signed to receive RT increased or at

least maintained their MVPA levels,
they would benefit from both RT and
aerobic MVPA. However, if RT inhib-
ited participants from achieving rec-
ommended MVPA levels, the net re-
sult could interfere with exercise
interventions aimed at improving
cardiovascular function, insulin ac-
tion, energy metabolism, and psy-
chological health in patients with OA
of the knee.13,14 Therefore, in the
present analysis, we aimed to deter-
mine the effect of a structured RT
intervention on overall daily levels of
activity by using accelerometry to
measure MVPA in individuals with
early-onset knee OA who partici-
pated in an RT program and in those
who participated in an SM program.
We hypothesized that in addition to
improving muscle strength (force-
generating capacity), the RT groups
would maintain similar levels of
MVPA compared with the SM group.

Method
Design Overview
The data used for this analysis were
obtained from the Multidimensional
Intervention for Early Osteoarthritis
of the Knee Study (the Knee Study),
a randomized clinical trial comparing
the effectiveness of SM alone, RT
alone, and combined RT�SM on rel-
evant knee OA outcomes over 24
months. After preliminary analyses
of the 3 groups, the RT groups (RT
alone and RT�SM) were collapsed
into a single group and compared
with the SM only group to test the

* 1 MET�3.5 mL O2�kg
�1�min�1.

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Effects of Resistance Training on Physical Activity

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http://ptjournal.apta.org/cgi/content/full/90/3/356/DC1

http://ptjournal.apta.org/cgi/content/full/90/3/DC1

http://ptjournal.apta.org/cgi/content/full/90/3/DC1

question of whether participants ran-
domly assigned to the RT group
would substitute RT for MVPA. The
analysis presented here was based
on data from the first phase (baseline
to 9 months) of the interventions
described. Outcome measurements
were obtained at baseline and at 3
and 9 months of intervention.

Participants
Participants were recruited from the
Tucson, Arizona, general community
and surrounding areas using mass
mailings, media advertisements, pe-
riodic media coverage, and requests
to local physicians for patient refer-
rals. A total of 1,726 people were
assessed for eligibility. Eligibility cri-
teria were: age between 35 and 68
years to ensure an early-onset knee
OA sample; pain on 4 or more days
of the week in one or both knees for
at least 4 months during the previous
year; less than 5 years’ symptom du-
ration15,16; radiographic status of
grade II OA (and no higher) in at
least one knee, as defined by the
Kellgren and Lawrence classifica-
tion17; and disability due to knee OA,
as assessed with the Western Ontario
and McMaster Universities Osteo-
arthritis (WOMAC) Index.18 Partici-

pants gave written informed consent
and self-reported demographic char-
acteristics (Tab. 1). All participants
enrolled in the study met American
College of Rheumatology classifica-
tion criteria for early OA of the
knee.19

A CONSORT flowchart describing
the progress of participants through
the 9-month intervention is pre-
sented in Figure 1. Of the 1,726 peo-
ple who were assessed for eligibility,
293 eligible participants were strati-
fied by sex and randomly assigned
via a random number table to 1 of
the 3 treatment groups (SM, RT, or
RT�SM). Concealed allocation was
accomplished using envelopes to
conceal computer-generated values.
Manifest transparency of the treat-
ments rendered blinding unfeasible.
Essentially, given our outcome mea-
sures, interrater agreement bias was
deemed a smaller threat to internal
validity than ensuring treatment fi-
delity, which precluded effective
blinding. Of the 293 eligible partici-
pants, 39 did not receive any of the
allocated intervention and 33 discon-
tinued the intervention prior to 9
months (Fig. 1).

Interventions
Resistance training. The overall
goal of the RT intervention was to
encourage participants to maintain a
long-term exercise program to in-
crease muscle strength, decrease im-
pairment, maintain and restore func-
tion, and protect joint structures
from further damage. The RT inter-
vention paralleled programs devel-
oped by the ACSM5 and the National
Strength Training and Conditioning
Association20 and was designed to
test expert panel recommenda-
tions.8 Sessions targeted improve-
ment in each of 4 core areas: (1)
stretching and balance, (2) range of
motion (ROM) and flexibility, (3) iso-
tonic muscle strengthening, and (4)
aerobics. Participants met with cer-
tified physical trainers 3 times per
week for 9 months, with a minimum
of 1 day of rest between training ses-
sions, to complete a 1-hour exercise
regimen that emphasized RT. Super-
vised, small-group sessions were
held to improve adherence. Each ses-
sion consisted of: (1) 10-minute
warm-up on either a bicycle ergome-
ter or treadmill at 50% maximum
heart rate, (2) 5 to 10 minutes of
stretching and balance exercises, (3)
10 minutes of ROM exercises, (4) 30

Table 1.
Baseline Descriptive Characteristics of Participants by Intervention Groupa

Characteristic
SM Group

(n�57)

RT Group
(n�52)

RT�SM
Group
(n�62)

Collapsed RT
and RT�SM Group

(n�114)

Noncompleters

(n�83)

Female (%) 72 73 79 76 83

Age (y), X (SD) 55.8 (6.1) 55.5 (7.3) 54.2 (7.3) 54.7 (7.3) 55.5 (7.7)

Height (cm), X (SD) 169.5 (8.1) 169.6 (10.6) 167.2 (9.4) 168.3 (10.0) 166.7 (10.1)

Weight (kg), X (SD) 80.6 (13.7) 80.1 (19.4) 76.1 (13.4) 77.8 (16.6) 78.2 (15.2)

BMI (kg/m2), X (SD) 28.0 (4.0) 27.5 (4.5) 27.2 (4.2) 27.3 (4.3) 28.1 (4.3)

Normal (�25) 30% 35% 32% 33% 33%

Overweight (25–30) 40% 36% 40% 39% 39%

Obese (�30) 30% 29% 28% 28% 28%

Knee OA severity

Grade 11 unilateral knee OA 59% 46% 56% 52% 55%

Grade II bilateral knee OA 41% 54% 44% 48% 45%

a SM�self-management, RT�resistance training, RT�SM�resistance training � self-management, BMI�body mass index, OA�osteoarthritis.

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Figure 1.
Flowchart describing the progress of participants through the Knee Study trial. RT�resistance training, SM�self-management,
RT�SM�resistance training � self-management.

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minutes of RT exercises, and (5) 5
minutes of cool-down. Specific RT
exercises included leg press, leg
curl, hip abduction and adduction,
straight leg lift, incline dumbbell
press, seated row, and calf raise. The
exercises were chosen primarily to
directly strengthen the muscles sup-
porting the knee, but also to im-
prove the strength of muscles most
involved in activities of daily living.

The strength protocol progressed
through 2 phases: (1) resistance
from body weight and Thera-Band
exercise bands† and (2) free weights
and machine weights. Participants
started with one set per exercise, 6
to 8 repetitions per set, at an inten-
sity of 50% of each individual’s
3-repetition maximum (3-RM). Dur-
ing an orientation session, partici-
pants were familiarized with the
equipment and instructed by certi-
fied trainers on proper lifting tech-
niques for all exercises. All partici-
pants began training at a comfortable
weight with proper form for each
exercise based on standardized pro-
tocols developed by the ACSM.5 The
program progressed from 1 to 2 sets,
along with increases in load when
participants were able to complete
all repetitions with proper body po-
sition and joint alignment for 3 con-

secutive sessions.21 They then pro-
gressed to loads between 60% and
75% of their 3-RM and continued to
increase loads to maintain vigorous
intensity. The ROM exercises were
increased for each participant when
the exercises could be completed
with a Borg scale score of difficulty
of �6.22 Participants completed
training logs during all sessions and
reported sets, repetitions, and loads
for each exercise. Certified physical
trainers supervised all RT sessions,
monitored progression, and tested
participants following standard pro-
tocols.5 Throughout the interven-
tion, trainers emphasized good form
and encouraged participants to re-
port soreness or pain during and af-
ter RT sessions. Changes in load from
baseline to 9 months for the RT
groups (RT and RT�SM) are shown
in Table 2.

Self-management. The SM inter-
vention was designed to target cop-
ing skills, promoting the use of more
adaptive strategies and fewer avoid-
ance or passive strategies based on
existing self-help programs.23 The in-
tervention also targeted self-efficacy
through a variety of educational and
behavioral techniques. Self-efficacy
skills focused on increasing percep-
tions of control for physical function-
ing, pain management, and other
ancillary arthritis symptoms. The

9-month program began with 12
weekly, 90-minute classroom ses-
sions in which participants com-
pleted SM education modules ad-
dressing an overview of OA, general
exercise principles and PA recom-
mendations, stress management,
foot care, pain management, analge-
sic and anti-inflammatory medica-
tions, nutrition for health, coping
mechanisms, communication with
health care providers, and healthy
lifestyle practices. As part the of the
exercise module, participants were
introduced to the benefits of MVPA
and RT for patients with OA of the
knee and were given instructions for
establishing a regular PA program.
They also were provided with PA
recommendations implemented by
the CDC6 and the ACSM5 and work
group PA recommendations from
the 2002 EPAC for people with ar-
thritis,7 but no further exercise in-
struction was given. Classroom ses-
sions were followed by 24 weeks of
a structured telephone intervention
program that reinforced SM skills.

Combined treatment. The com-
bined treatment group (RT�SM) en-
gaged in both the RT and SM inter-
ventions, with slight alterations to
ensure equivalence of contact time
across treatment groups. Specifi-
cally, participants in the RT�SM
group were contacted by staff less
during the 24 weeks of the tele-
phone intervention program that fol-
lowed classroom sessions.

Anthropometry. Anthropometric
measurements were obtained at
baseline following standard proto-
cols outlined in the Anthropometric
Standardization Reference Manu-
al.24 Total body mass was measured
to the nearest 0.1 kg using a cali-
brated scale (Seca model 770),‡ and
height was measured to the nearest
0.1 cm using a portable stadiometer

† The Hygenic Corp, 1245 Home Ave, Akron,
OH 44310-2575.

‡ Seca GMBH and Co KG, Hammer Steindamm
9 25, 20089 Hamburg, Germany.

Table 2.
Change (�) in Weight Lifted From Baseline to 9 Months of Intervention for All
Resistance Trainersa

Exercise
RT

Group �
RT�SM
Group �

All
(n�114) � P b

Leg press 112.7 (72.1) 91.9 (67.3) 101.6 (69.3) .19

Incline dumbbell press 11.4 (8.5) 10.7 (8.0) 11.0 (8.2) .69

Seated row 27.2 (15.8) 20.1 (18.2) 23.3 (17.4) .08

Leg curl 41.2 (35.5) 33.7 (39.6) 37.3 (37.7) .40

Calf raise 13.4 (15.1) 10.9 (15.2) 12.2 (15.0) .60

a Values are means (SD) for change in load (pounds) from baseline to 9 months of intervention based
on 1 to 2 sets of 6 to 8 repetitions. RT�resistance training, RT�SM�resistance training �
self-management.
b Independent t test for group difference.

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(Shorr Height Measuring Board)§ af-
ter full inspiration.

Pain. Knee pain was assessed us-
ing the WOMAC Index, which has
been validated in patients with OA of
the knee.18 The WOMAC pain sub-
scale comprises 5 items eliciting pa-
tient ratings on visual analog scales
(0 –100) of pain severity during walk-
ing, stair use, lying in bed at night,
sitting, and standing. The pain sub-
scale has a maximum summed score
of 500, with higher scores reflecting
more pain.

Physical activity. Baseline PA lev-
els of the Knee Study participants
have been published previously.25

Physical activity was measured using
the MTI Actigraph accelerometer
(model 7164).� The uniaxial Acti-
graph accelerometer measures
vertical-plane accelerations and de-
celerations and records them as
“counts” over a specific time interval
(epoch), which provides informa-
tion regarding the intensity of PA as-
sociated with movement.26 The ac-
celerometer assesses accelerations
ranging from 0.05 to 2.0g, with a
frequency ranging from 0.25 to 2.5
Hz.27 These specifications allow for
detection of normal body motion,
while filtering out high-frequency vi-
bration movements. Actigraph reli-
ability and validity have been re-
viewed in detail.28 Counts have been
shown to be highly correlated
(r�.77–.88) with steady-state oxy-
gen consumption during ambulatory
activities26,29 and have been shown
to be dependent upon movement
frequency in a mechanical setup.30

For each assessment, the accelerom-
eter was initialized and downloaded
according to the manufacturer’s
specifications30 and set to record

data in 60-second epochs. Partici-
pants were instructed to wear the
accelerometer for 7 contiguous days
during all waking hours, except
while in water. A previous study31

has shown that when the Actigraph
accelerometer is worn for 7 consec-
utive days, PA can be assessed with
90% reliability. The accelerometer
was firmly secured to a belt worn
around the waist and positioned on
the right hip because this site per-
mits measurement of whole-body
movement, does not interfere with
daily activities, and is the most fre-
quently used site in epidemiological
studies.25 The following measure-
ments were obtained: days worn;
registered wear time in hours per
day; and average minutes per day
spent in moderate-intensity physical
activity (MPA, 3– 6 METs), vigorous-
intensity physical activity (VPA, �6
METs), and MVPA (�3 METs). A
number of studies26,29,32–34 have
used criterion methods such as indi-
rect calorimetry and heart rate mon-
itoring to demonstrate the reliability
and validity of the Actigraph acceler-
ometer. As described in detail previ-
ously,25 we minimized sampling
error by averaging the cutoff points
reported by calibration studies us-
ing the MTI Actigraph model
716426,29,32–34 and applied the result-
ing cutoff points to differentiate
among PA intensities. The applied
cutoff points for MPA and VPA inten-
sities were accelerometer recordings
of 2,225 to 5,950 and �5,950 counts
per minute, respectively. Moderate-
and vigorous-intensity physical activ-
ity was defined as �2,225 counts per
minute.

Leisure time PA and exercise habits
were assessed at baseline and at 3
and 9 months of intervention using
the Aerobics Center Longitudinal
Study Physical Activity Question-
naire (ACLS).35 The ACLS elicits self-
reports of frequency (sessions per
week) and duration (minutes per ses-
sion) of activities such as walking,

running, treadmill, cycling, swim-
ming, aerobics, yoga, weight lifting,
and other sports (eg, golf, tennis,
soccer).

Data Analysis
For the analyses presented here, a
valid day of PA was defined as having
10 or more hours of accelerometer
wearing, based on previous recom-
mendations from analyses of the
National Health and Nutrition Exam-
ination Survey (NHANES) accelerom-
eter database.36 Furthermore, 5 to 7
days of valid accelerometer wearing
was required for inclusion in the
present analysis. We chose a mini-
mum of 5 days of accelerometer
wearing because PA levels vary
greatly throughout the week and 1 to
4 days of PA may not be representa-
tive of habitual PA.28

In order to address the question of
whether participants randomly as-
signed to receive RT would substi-
tute RT for MVPA, the RT groups (RT
and RT�SM, n�114) were collapsed
into a single group and compared
with the SM group (Tab. 1). Descrip-
tions of the 171 participants ran-
domly assigned to each of the 3 in-
tervention groups (SM, RT, RT�SM)
and the 114 participants who re-
ceived the RT intervention (col-
lapsed RT and RT�SM group) are
shown in Table 1. Means, standard
deviations, and 95% confidence in-
tervals were calculated for continu-
ous variables, and frequencies were
calculated for categorical variables.
Data were checked for missing
values and normality prior to analy-
ses. Moderate- and vigorous-intensity
physical activity (minutes per day),
which was skewed, was natural log
transformed for analysis, resulting in
a normal distribution.

Preliminary tests for baseline differ-
ences in descriptive characteristics
among the 3 intervention groups
were performed using an analysis of
variance or the chi-square test for

§ Shorr Productions, 17802 Shotley Bridge
Place, Olney, MD 20832.
� Manufacturing Technologies Inc, 70 Ready
Ave NW, Fort Walton Beach, FL 32548.

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proportions as appropriate. For all
subsequent analyses, the RT groups
(RT and RT�SM) were collapsed
into a single group and compared
with the SM group to address the
question of whether RT affects
MVPA. The RT groups were com-
bined because both groups of partic-
ipants engaged in the RT interven-
tion and no significant (P�.05)
group differences using independent
t tests were observed for any vari-
ables at any time point. Effect sizes
representing the magnitude of differ-
ence between baseline and 3 and 9
months were calculated using Co-
hen’s method37 based on adjusted
means of MVPA for the 2 groups (SM
and collapsed RT).

A repeated-measures analysis of co-
variance was performed with group
(SM and collapsed RT) as the
between-subjects factor and time (3
and 9 months) as the within-subjects
factor. Baseline MPVA, age, BMI,
knee OA pain, and sex were entered
as covariates to account for baseline
between-group differences in MVPA
and the putative influence of these
variables on MVPA. The specific ef-
fect of interest in this analysis was
the group � time interaction. A sig-
nificant group � time interaction
would indicate that the degree of
change in MVPA over time was dif-
ferent for the 2 groups (SM and col-
lapsed RT). Statistical significance
was set at P�.05 for all tests. Analy-
ses were conducted using the Statis-
tical Package for the Social Sciences,
version 17.0.#

Results
At baseline, 3 months, and 9 months,
5, 17, and 26 participants, respec-
tively, either did not wear an accel-
erometer or did not meet the inclu-
sion criteria. Comparisons of
baseline descriptive characteristics
for noncompleters (n�83) versus

completers (n�171) showed no sig-
nificant (P�.05) differences (Tab. 1).
After 9 months of intervention, the
numbers of participants who suc-
cessfully completed all measures at
baseline, 3 months, and 9 months
were as follows: SM group�57, RT
group�52, RT�SM group�62
(Fig. 1). The final sample of partici-
pants with early onset OA of the
knee who successfully adhered to
the accelerometer protocol com-
prised 171 participants (74%
women, 26% men; mean age�55.1
(SD�7.1) years, and mean BMI�27.6
(SD�4.2) kg/m2). Preliminary base-
line analyses of the 3 intervention
groups showed no significant
(P�.05) difference among groups or
between completers (n�171) and
noncompleters (n�83) at baseline
for any variables (Tabs. 1 and 3). Par-
ticipants wore the accelerometer, on
average, 6.8 (SD�0.5) days and 14.2
(SD�2.2) hours per day over all 3 PA
assessments. There were no signifi-
cant group differences (P�.05) in
number of days the accelerometer
was worn or in accelerometer wear-
ing time at any time interval. Signifi-
cant differences were not observed
for any of the measured variables
(P�.05) when participants with 5 to
6 days of accelerometer data were
compared with participants with 7
days of data. Unadjusted means, stan-
dard deviations, and 95% confidence
intervals for MPA, VPA, and MVPA
for the collapsed RT group and the
SM group at baseline, 3 months, and
9 months are presented in Table 3.

Exercise session attendance was
75.9% (SD�17.9%) for the collapsed
RT group, and SM class attendance
was 85.9% (SD�14.2%) for the SM
group. However, attendance did not
significantly (P�.48) differ between
the collapsed RT group and the SM
group. The RT groups significantly
(P�.001) increased their leg press,
leg curl, incline dumbbell press,
seated row, and calf raise loads from
baseline to 9 months (Tab. 2). Data

from the ACLS questionnaire
showed that few SM group partici-
pants (n�11, 19%) reported engag-
ing in any form of resistance exercise
throughout the intervention.

Despite high exercise session atten-
dance and significant improvements
in muscle strength, very little time
(minutes per day) was spent in VPA
as measured by the accelerometer,
and there were no significant
(P�.05) differences in VPA among
the intervention groups at any time
interval (Tab. 3). Consequently, aver-
age daily MVPA (�3 METs) was rep-
resentative of total time spent in
health-enhancing PA intensities. The
collapsed RT group participants in-
creased their MVPA by 18% at 3
months (P�.001, effect size [d]�
0.26) and by 10% at 9 months
(P�.047, effect size [d]�0.15) com-
pared with baseline levels. The SM
group participants increased their
MVPA by 22% at 3 months (P�.023,
effect size [d]�0.25) and by 2% at 9
months (P�.80, effect size
[d]�0.03) compared with baseline
levels. After adjusting for baseline
MVPA, age, BMI, sex, and knee OA
pain, there was a significant
(P�.034) group � time interaction
for MVPA, which indicated that lon-
gitudinal MVPA decreased at a
greater rate in the SM group than in
the collapsed RT group (Fig. 2).

Discussion
The overall increase in MVPA by the
RT groups suggests that patients
with early-onset OA of the knee can
engage in a structured resistance
exercise program without a compen-
satory decrease in MVPA levels.
Compared with baseline, MVPA in-
creased in the collapsed RT group by
18% at 3 months and 10% at 9
months, and the SM group showed a
22% increase in MVPA at 3 months
but only a 2% increase at 9 months.
These findings indicate that both SM
and RT programs are effective for
increasing short-term MVPA in pa-

# SPSS Inc, 233 S Wacker Dr, Chicago, IL
60606.

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tients with early OA of the knee,
which is consistent with the findings
of previous studies.38 – 40 The greater
3-month increase in MVPA in the SM
group compared with the RT group
may have resulted from differences
in adherence (SM group�86%, RT
group�76%) or because both pro-
grams encouraged PA. Although
both treatments were effective in in-
creasing short-term MVPA, RT was
better than SM for maintaining long-
term MVPA levels. Indeed, a signifi-
cant group � time interaction indi-
cated that the degree of change in
MVPA was different between groups
(ie, MVPA in the RT groups re-
gressed between 3 and 9 months at a
slower rate than in the SM group).
Thus, rather than simply substituting
RT for MVPA, the RT groups were

able to maintain MVPA levels in ad-
dition to attaining strength benefits
from RT. It is possible that participa-
tion in the RT sessions may have con-
tributed to the long-term mainte-
nance of MVPA levels. On the other
hand, adherence and MVPA in the
SM group may have dropped off be-
cause of the intervention content.
For example, early sessions focused
on developing SM skills, whereas
later sessions focused on reinforcing
those skills. Thus, those participants
who already mastered the skills may
have seen less utility in the contin-
ued support.

Previous studies have shown that
when older adults participate in
structured RT programs, there is a
tendency for a compensatory de-

crease in aerobic MVPA.11,12 For ex-
ample, Goran and Poehlman11 ob-
served a decrease of �544 kJ per day
in free-living PA in elderly adults
who were healthy after an 8-week
high-intensity (85% of maximal oxy-
gen consumption) training program.
It is possible that the high intensity
of the exercise program used in that
study was too vigorous, thereby fa-
tiguing the participants to the extent
that they were no longer able to en-
gage their regular PA throughout the
remainder of the day. Meijer et al12

reported that a 12-week, moderate-
intensity combined aerobic and RT
program resulted in improved phys-
ical fitness but had no effect on total
daily PA (ie, after subtracting the PA
of the exercise training sessions, this
study showed that training PA was

Table 3.
Means (SD) and 95% Confidence Intervals for Average Time Spent in the 3 Physical Activity Intensities and for Knee
Osteoarthritis Paina

Measure

SM Group
(n�57)

RT Group
(n�52)

RT�SM Group
(n�62)

Collapsed RT and
RT�SM Group

(n�114)

X (SD) [95%CI] X (SD) [95%CI] X (SD) [95%CI] X (SD) [95%CI]

MPAb (min/d)

Baseline 23.4 (18.2) [18.9–28.6] 24.6 (17.8) [19.8–29.7] 27.9 (18.3) [23.2–32.6] 26.5 (18.1) [23.1–29.8]

3 mo 29.0 (22.5) [23.1–35.0] 27.9 (19.4) [23.1–32.7] 32.1 (17.1) [27.7–36.4] 30.2 (17.2) [27.0–33.4]

9 mo 24.1 (17.5) [19.4–28.7] 26.1 (17.7) [21.2–31.1] 30.1 (15.0) [26.3–33.9] 28.3 (16.3) [25.3–31.3]

VPAc (min/d)

Baseline 0.8 (2.9) [0.0–1.6] 0.8 (2.6) [0.1–1.6] 1.0 (2.0) [0.5–1.5] 0.9 (2.3) [0.5–1.4]

3 mo 0.7 (1.7) [0.3–1.2] 2.1 (4.9) [0.7–3.5] 1.6 (2.5) [0.9–2.2] 1.8 (3.8) [1.1–2.5]

9 mo 0.7 (2.1) [0.1–1.2] 1.6 (4.2) [0.4–2.8] 1.9 (3.7) [26.3–33.9] 1.8 (4.0) [1.0–2.5]

MVPAd (min/d)

Baseline 24.2 (19.3) [19.4–29.7] 25.4 (19.4) [20.2–31.0] 28.6 (19.4) [24.0–33.8] 27.4 (19.4) [23.8–31.0]

3 mo 29.7 (23.1) [23.6–35.9] 30.0 (19.7) [24.5–33.3] 33.6 (18.2) [29.0–38.3] 32.0 (18.9) [28.5–35.5]

9 mo 24.8 (18.7) [19.7–29.6] 27.7 (20.0) [22.2–33.3] 31.8 (16.8) [27.7–36.2] 30.1 (18.3) [26.7–33.5]

Knee OA paine

Baseline 82.2 (68.3) [64.1–100.3] 84.3 (70.1) [64.8–103.8] 81.9 (67.3) [64.8–99.0] 83.0 (68.3) [70.3–95.6]

3 mo 72.0 (66.3) [54.4–89.6] 47.6 (50.9) [33.5–61.8] 67.1 (68.8) [49.5–84.7] 58.2 (61.8) [46.6–69.7]

9 mo 62.9 (81.0) [41.4–84.4] 48.6 (61.3) [31.4–65.9] 56.2 (75.3) [36.7–75.6] 52.7 (29.1) [39.7–65.7]

a SM�self-management, RT�resistance training, RT�SM�resistance training � self-management, CI�confidence interval, OA�osteoarthritis.
b MPA�moderate-intensity physical activity (3– 6 metabolic equivalents [METs]).
c VPA�vigorous-intensity physical activity (�6 METs).
d MVPA�combined moderate- and vigorous-intensity physical activity (�3 METs).
e Knee OA pain assessed with Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index pain subscale comprising 5 items eliciting patient
ratings on visual analog scale (0 –100) of pain severity during walking, stair use, lying in bed at night, sitting, and standing. The pain subscale has a
maximum summed score of 500, with higher scores reflecting more pain.

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compensated for by a decrease in
nontraining PA, consistent with the
findings of Goran and Poehlman11).
In contrast, a 26-week RT program in
a study by Hunter et al10 was not
associated with a compensatory
drop in free-living PA. The findings
of Hunter et al are consistent with
our findings because participants
were able to engage in RT without
substituting RT for MVPA.

Although accelerometers allow for
accurate measurements of daily time
spent in various health-enhancing PA
intensities (ie, MPA, VPA, and
MVPA),26 hip placement may under-
estimate energy expenditure during
certain activities (ie, biking, climbing
stairs, and weight lifting) and pro-
vide no estimate of PA during water
activities (eg, swimming) because ac-
celerometers cannot be worn.28

Given the time spent standing, sit-
ting, and lying during RT, this mode
of activity is not measured well by
accelerometers.28 This finding was
evident in the present study because

despite rather high exercise session
attendance (RT group�76%) and sig-
nificant (P�.001) increases in load
from baseline to 9 months for a num-
ber of RT exercises (eg, leg press, leg
curl, seated row, incline dumbbell
press, calf raise), average daily VPA
in the RT group remained extremely
low at 3 months (1.8 [SD�3.8] min-
utes per day) and 9 months (1.8
[SD�4.0] minutes per day). Thus,
based on the observed improve-
ments in strength, the RT groups
likely received additional benefits of
RT compared with the SM group,
such as improved REE, TEE, AEE,
lipid oxidation rates, musculoskele-
tal function, and body composition,
which have been observed in re-
sponse to RT in older adults.9,10,41

Furthermore, the ACLS question-
naire indicated that few SM group
participants (n�11, 19%) engaged in
any form of RT, and thus the majority
of participants in this group did not
receive additional benefits of RT.

In addition to increasing TEE,10 RT
has been shown to improve a num-
ber of functional limitations that lead
to disability in patients with OA of
the knee, such as quadriceps muscle
weakness,42 neurological deficits,43

and decreased knee ROM.44 Further-
more, RT programs have been
shown to improve psychological fac-
tors such as mood, self-efficacy, anx-
iety, and depression.45,46 Aerobic
MVPA also can improve some of the
same functional limitations in pa-
tients with OA of the knee and can
reduce risks of obesity-linked health
problems, including diabetes and
cardiovascular disease,5,6 which of-
ten coexist with knee OA. There-
fore, in clinical settings, the ability to
engage in RT without sacrificing
MVPA is important.

We acknowledge several limitations
of our study. For example, 5 to 7
days of contiguous accelerometer re-
cordings may not be representative
of habitual PA, and adipose tissue
around the waist might affect the
validity of the accelerometer out-
puts.25 Furthermore, accelerometers
may underestimate PA during activi-
ties such as biking, climbing stairs,
and weight lifting and cannot be
worn during water activities (eg,
swimming).28 Thus, PA may be un-
derestimated in individuals who en-
gage in these activities on a regular
basis. More detailed physiological
studies are needed in patients with
OA of the knee to measure directly
different energy expenditures (ie,
REE, TEE, and AEE), which have
been shown to be elevated in older
adults in response to RT.9,10 Lastly,
we cannot establish a causal relation-
ship between increased levels of
MVPA and improved physical func-
tion because we did not measure
functional changes. However, a
number of randomized controlled
trials8,39,40,47,48 in patients with OA of
the knee have shown a strong asso-
ciation between increased levels of
MVPA and RT and improved physical

Figure 2.
Average daily moderate- and vigorous-intensity physical activity (MVPA, �3 metabolic
equivalents) at 3 and 9 months of intervention for the self-management group (SM)
and collapsed resistance training (RT) groups (RT and RT�SM). Values were adjusted for
baseline MVPA, age, body mass index, sex, and knee osteoarthritis pain. There was a
significant group � time interaction (P�.034) for MVPA.

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function, which provides support
for improved knee function of indi-
viduals who undertook the RT
intervention.

Conclusion
Patients with early-onset knee OA
were able to engage in an RT pro-
gram without a compensatory de-
crease in their overall MVPA levels.
Because RT has been shown to in-
crease energy expenditure in
adults9,10,41 and has been shown to
improve muscle strength and physi-
cal function and to reduce pain in
patients with OA of the knee,8 it is a
vital component of knee OA therapy.
Given the relevant health benefits of
RT and aerobic MVPA for manage-
ment of knee OA, future studies are
necessary to improve adherence to
both modes of exercise.

Dr Going and Dr McKnight provided con-
cept/idea/research design. Mr Farr, Dr Mc-
Knight, and Dr Kasle provided writing. Mr
Farr, Dr McKnight, Dr Kasle, and Dr Cornett
provided data collection. Dr Kaske provided
data management. Mr Farr, Dr McKnight,
and Ms Cussler provided data analysis. Dr
Going, Dr McKnight, and Dr Cornett pro-
vided project management. Dr McKnight
provided fund procurement. Dr Going and
Ms Cussler provided consultation (including
review of manuscript before submission).

The authors thank the men and women with
knee OA who generously volunteered their
time, the project coordinators for their over-
sight of all aspects of the study, and the
other members of the Knee Study investiga-
tive team. Dr Isidro Villanueva is gratefully
acknowledged for his contributions to the
Knee Study.

This study was approved by the University of
Arizona Institutional Review Board and con-
ducted in accordance with the Helsinki
Declaration.

This project was supported by National In-
stitutes of Health/National Institute of Arthri-
tis and Musculoskeletal and Skin Diseases
grant R01-AR-047595. The content is solely
the responsibility of the authors and does
not necessarily represent the official views of
the National Institute of Arthritis and Mus-
culoskeletal and Skin Diseases or the Na-
tional Institutes of Health.

NIH Clinical Trials Registry: NCT00586300.

This article was received February 10, 2009,
and was accepted October 30, 2009.

DOI: 10.2522/ptj.20090041

References
1 Mazzuca SA. Is behavioral graded activity

effective for the treatment of hip and knee
osteoarthritis? Nat Clin Pract Rheumatol.
2007;3:322–323.

2 American College of Rheumatology Sub-
committee on Osteoarthritis Guidelines.
Recommendations for the medical man-
agement of osteoarthritis of the hip and
knee: 2000 update. Arthritis Rheum.
2000;43:1905–1915.

3 Jordan KM, Arden NK, Doherty M, et al.
EULAR Recommendations 2003: an
evidence-based approach to the manage-
ment of knee osteoarthritis: Report of a
Task Force of the Standing Committee for
International Clinical Studies Including
Therapeutic Trials (ESCISIT). Ann Rheum
Dis. 2003;62:1145–1155.

4 Scott DL, Shipley M, Dawson A, et al. The
clinical management of rheumatoid arthri-
tis and osteoarthritis: strategies for im-
proving clinical effectiveness. Br J Rheu-
matol. 1998;37:546 –554.

5 American College of Sports Medicine Po-
sition Stand: The recommended quantity
and quality of exercise for developing and
maintaining cardiorespiratory and muscu-
lar fitness, and flexibility in healthy adults.
Med Sci Sports Exerc. 1998;30:975–991.

6 US Department of Health and Human Ser-
vices. Physical Activity and Health: A Re-
port of the Surgeon General. Atlanta, GA:
Centers for Disease Control and Preven-
tion, National Center for Chronic Disease
Prevention and Health Promotion; 1996.

7 Minor MA. 2002 Exercise and Physical Ac-
tivity Conference, St Louis, Missouri: exer-
cise and arthritis “we know a little bit
about a lot of things em leader.” Arthritis
Rheum. 2003;49:1–2.

8 Roddy E, Zhang W, Doherty M, et al.
Evidence-based recommendations for the
role of exercise in the management of os-
teoarthritis of the hip or knee: the MOVE
consensus. Rheumatology (Oxford).
2005;44:67–73.

9 Withers RT, Smith DA, Tucker RC, et al.
Energy metabolism in sedentary and active
49- to 70-year-old women. J Appl Physiol.
1998;84:1333–1340.

10 Hunter GR, Wetzstein CJ, Fields DA, et al.
Resistance training increases total energy
expenditure and free-living physical activ-
ity in older adults. J Appl Physiol. 2000;
89:977–984.

11 Goran MI, Poehlman ET. Endurance train-
ing does not enhance total energy expen-
diture in healthy elderly persons. Am J
Physiol. 1992;263(5 pt 1):E950 –E957.

12 Meijer EP, Westerterp KR, Verstappen FT.
Effect of exercise training on total daily
physical activity in elderly humans. Eur
J Appl Physiol Occup Physiol. 1999;80:
16 –21.

13 Booth FW, Gordon SE, Carlson CJ, Hamil-
ton MT. Waging war on modern chronic
diseases: primary prevention through ex-
ercise biology. J Appl Physiol. 2000;88:
774 –787.

14 Pate RR, Pratt M, Blair SN, et al. Physical
activity and public health: a recommenda-
tion from the Centers for Disease Control
and Prevention and the American College
of Sports Medicine. JAMA. 1995;273:
402– 407.

15 Hart DJ, Spector TD, Brown P, et al. Clin-
ical signs of early osteoarthritis: reproduc-
ibility and relation to x-ray changes in 541
women in the general population. Ann
Rheum Dis. 1991;50:467– 470.

16 Sullivan T, Allegrante JP, Peterson MG,
et al. One-year followup of patients with
osteoarthritis of the knee who partici-
pated in a program of supervised fitness
walking and supportive patient education.
Arthritis Care Res. 1998;11:228 –233.

17 Kellgren JH, Lawrence JS. Radiological as-
sessment of osteo-arthrosis. Ann Rheum
Dis. 1957;16:494 –502.

18 Bellamy N, Buchanan WW, Goldsmith CH,
et al. Validation study of WOMAC: a health
status instrument for measuring clinically
important patient relevant outcomes to
antirheumatic drug therapy in patients
with osteoarthritis of the hip or knee.
J Rheumatol. 1988;15:1833–1840.

19 Altman R, Asch E, Bloch D, et al; for the
Diagnostic and Therapeutic Criteria Com-
mittee of the American Rheumatism Asso-
ciation. Development of criteria for the
classification and reporting of osteoarthri-
tis: classification of osteoarthritis of
the knee. Arthritis Rheum. 1986;29:
1039 –1049.

20 Pearson D, Faigenbaum A, Conley M, Krae-
mer WJ. The National Strength and Condi-
tioning Association’s basic guidelines for
the resistance training of athletes.
Strength and Conditioning Journal.
2000;22:14 –27.

21 Baker KR, Nelson ME, Felson DT, et al.
The efficacy of home based progressive
strength training in older adults with knee
osteoarthritis: a randomized controlled tri-
al. J Rheumatol. 2001;28:1655–1665.

22 Borg GA. Psychophysical bases of per-
ceived exertion. Med Sci Sports Exerc.
1982;14:377–381.

23 Lorig KR, Holman H. Self-management ed-
ucation: history, definition, outcomes, and
mechanisms. Ann Behav Med. 2003;26:
1–7.

24 Lohman TG, Roche AF, Martorell R. An-
thropometric Standardization Reference
Manual. Champaign, IL: Human Kinetics
Publishers; 1988.

25 Farr JN, Going SB, Lohman TG, et al. Phys-
ical activity levels in patients with early
knee osteoarthritis measured by accelerom-
etry. Arthritis Rheum. 2008;59:1229 –1236.

26 Freedson PS, Melanson E, Sirard J. Calibra-
tion of the Computer Science and Appli-
cations Inc accelerometer. Med Sci Sports
Exerc. 1998;30:777–781.

27 Tryon W, Williams R. Fully proportional
actigraphy: a new instrument. Behav Res
Meth Instrum Comput. 1996;28:392– 403.

Effects of Resistance Training on Physical Activity

March 2010 Volume 90 Number 3 Physical Therapy f 365

D
ow
nloaded from
https://academ
ic.oup.com
/ptj/article-abstract/90/3/356/2737792 by guest on 02 M
arch 2020

28 Matthew CE. Calibration of accelerometer
output for adults. Med Sci Sports Exerc.
2005;37(11 suppl):S512–S522.

29 Hendelman D, Miller K, Baggett C, et al.
Validity of accelerometry for the assess-
ment of moderate intensity physical activ-
ity in the field. Med Sci Sports Exerc. 2000;
32(9 suppl):S442–S449.

30 Computer Science and Applications Inc
Activity Monitor Operator’s Manual,
Model 7164, Release 1.04. Shalimar, FL:
Computer Science and Applications Inc;
1995.

31 Matthews CE, Ainsworth BE, Thompson
RW, Bassett DR Jr. Sources of variance in
daily physical activity levels as measured
by an accelerometer. Med Sci Sports Ex-
erc. 2002;34:1376 –1381.

32 Brage S, Wedderkopp N, Franks PW, et al.
Reexamination of validity and reliability of
the CSA monitor in walking and running.
Med Sci Sports Exerc. 2003;35:1447–1454.

33 Nichols JF, Morgan CG, Chabot LE, et al.
Assessment of physical activity with the
Computer Science and Applications Inc
accelerometer: laboratory versus field val-
idation. Res Q Exerc Sport. 2000;71:
36 – 43.

34 Yngve A, Nilsson A, Sjostrom M, Ekelund
U. Effect of monitor placement and of ac-
tivity setting on the MTI accelerometer
output. Med Sci Sports Exerc. 2003;35:
320 –326.

35 Kohl HW, Blair SN, Paffembarger RS, et al.
The Aerobics Center Longitudinal Study
Physical Activity Questionnaire: a collec-
tion of physical activity questionnaires for
health-related research. Med Sci Sports Ex-
erc. 1997;29(suppl):S10 –S14.

36 Troiano RP, Berrigan D, Dodd KW, et al.
Physical activity in the United States mea-
sured by accelerometer. Med Sci Sports
Exerc. 2008;40:181–188.

37 Cohen J. A power primer. Psychol Bull.
1992;112:155–159.

38 Evcik D, Sonel B. Effectiveness of a home-
based exercise therapy and walking pro-
gram on osteoarthritis of the knee. Rheu-
matol Int. 2002;22:103–106.

39 Kovar PA, Allegrante JP, MacKenzie CR,
et al. Supervised fitness walking in pa-
tients with osteoarthritis of the knee: a
randomized, controlled trial. Ann Intern
Med. 1992;116:529 –534.

40 Talbot LA, Gaines JM, Huynh TN, Metter
EJ. A home-based pedometer-driven walk-
ing program to increase physical activity
in older adults with osteoarthritis of the
knee: a preliminary study. J Am Geriatr
Soc. 2003;51:387–392.

41 Van Etten LM, Westerterp KR, Verstappen
FT, et al. Effect of an 18-week weight-
training program on energy expenditure
and physical activity. J Appl Physiol. 1997;
82:298 –304.

42 Schilke JM, Johnson GO, Housh TJ, O’Dell
JR. Effects of muscle-strength training on
the functional status of patients with os-
teoarthritis of the knee joint. Nurs Res.
1996;45:68 –72.

43 Hurley MV, Scott DL. Improvements in
quadriceps sensorimotor function and dis-
ability of patients with knee osteoarthritis
following a clinically practicable exer-
cise regime. Br J Rheumatol. 1998;37:
1181–1187.

44 Badley EM, Wagstaff S, Wood PH. Mea-
sures of functional ability (disability) in ar-
thritis in relation to impairment of range of
joint movement. Ann Rheum Dis. 1984;
43:563–569.

45 Byrne A, Byrne DG. The effect of exercise
on depression, anxiety and other mood
states: a review. J Psychosom Res. 1993;
37:565–574.

46 McAuley E, Shaffer S, Rudolph D. Physical
activity, aging, and psychological well-be-
ing. JAPA. 1995;3:67–96.

47 Ettinger WH Jr, Burns R, Messier SP, et al.
A randomized trial comparing aerobic ex-
ercise and resistance exercise with a
health education program in older adults
with knee osteoarthritis: the Fitness Ar-
thritis and Seniors Trial (FAST). JAMA.
1997;277:25–31.

48 Bautch JC, Malone DG, Vailas AC. Effects
of exercise on knee joints with osteoar-
thritis: a pilot study of biologic markers.
Arthritis Care Res. 1997;10:48 –55.

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Osteoarthritis and Cartilage 23 (2015) 507e515

Review

Current evidence on risk factors for knee osteoarthritis in older adults:
a systematic review and meta-analysis

V. Silverwood*, M. Blagojevic-Bucknall, C. Jinks, J.L. Jordan, J. Protheroe, K.P. Jordan
Arthritis Research UK Primary Care Centre, Primary Care Sciences, Keele University, Staffordshire, ST5 5BG, UK

a r t i c l e i n f o

Article history:
Received 7 August 2014
Accepted 25 November 2014

Keywords:
Osteoarthritis
Knee
Incidence/onset
Risk factors
Systematic review
Meta-analysis

* Address correspondence and reprint requests to
Research UK Primary Care Centre, Primary Care Scie
fordshire, ST5 5BG.

http://dx.doi.org/10.1016/j.joca.2014.11.019
1063-4584/© 2014 The Authors. Published by Elsevie
(http://creativecommons.org/licenses/by-nc-nd/

4.0/).

s u m m a r y

Osteoarthritis (OA) is a leading cause of pain and disability and leads to a reduced quality of life. The aim
was to determine the current evidence on risk factors for onset of knee pain/OA in those aged 50 and
over. A systematic review and meta-analysis was conducted of cohort studies for risk factors for the onset
of knee pain. Two authors screened abstracts and papers and completed data extraction. Where possible,
pooled odds ratios (OR) were calculated via random effects meta-analysis and population attributable
fractions (PAFs) derived. 6554 papers were identified and after screening 46 studies were included. The
main factors associated with onset of knee pain were being overweight (pooled OR 1.98, 95% confidence
intervals (CI) 1.57e2.20), obesity (pooled OR 2.66 95% CI 2.15e3.28), female gender (pooled OR 1.68, 95%
CI 1.37e2.07), previous knee injury (pooled OR 2.83, 95% CI 1.91e4.19). Hand OA (pooled OR 1.30, 95% CI
0.90e1.87) was found to be non-significant. Smoking was found not to be a statistically significant risk or
protective factor (pooled OR 0.92, 95% CI 0.83e1.01). PAFs indicated that in patients with new onset of
knee pain 5.1% of cases were due to previous knee injury and 24.6% related to being overweight or obese.
Clinicians can use the identified risk factors to identify and manage patients at risk of developing or
increasing knee pain. Obesity in particular needs to be a major target for prevention of development of
knee pain. More research is needed into a number of potential risk factors.
© 2014 The Authors. Published by Elsevie

r Ltd and Osteoarthritis Research S

ociety International. This is
an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/

4.0/).

Introduction

Osteoarthritis (OA) is a serious joint disease that leads to a
reduced quality of life. In 2003, OA was the sixth leading cause of
disability worldwide, and has been estimated to rise to the fourth
leading cause by 20201. A 2004 study carried out in a general
population estimated that the prevalence of symptomatic OA in
those aged 60 and above was 9.6% in men and 18% in women2.
Approximately 25% of adults aged over 55 report at least one
episode of knee pain each year, which is likely to reflect underlying
OA3. OA is commonly presented in general practice, over 7 years an
estimated 13% of older adults receive a diagnosis of OA4.

A systematic review and meta-analysis assessing observational
studies up to January 2008 identified a set of factors for which there
was consistent evidence for their association with onset of knee
OA5. These factors were obesity, hand OA, previous knee trauma,
older age and female gender. However there was limited evidence

: Dr. V. Silverwood, Arthritis
nces, Keele University, Staf-

r Ltd and Osteoarthritis Research S

regarding the importance of co-morbidities such as depression,
occupational and physical activities, and socio-demographic factors
such as social class.

The objective of this systematic review and meta-analysis was to
determine the current evidence on risk factors for onset of knee
pain/OA in those aged 50 and over. The review concentrated on
non-clinical risk factors such as body mass index (BMI) and age.
Some of these risk factors can be modified at an individual patient
level in order to minimise the risk of developing knee OA or knee
pain and therefore lead to an increased quality of life for patients. A
further aim was therefore to estimate the individual contribution of
identified risk factors to the population level of onset of knee OA.

Methods

Phase 1 e Systematic review and meta-analysis

Search strategy and study selection
A search of studies published between the start of each database

and December 2012 was conducted using bibliographic databases,
including MEDLINE, EMBASE, CINAHL and AMED. Search terms

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V. Silverwood et al. / Osteoarthritis and Cartilage 23 (2015) 507e515508

included terms for knee OA/pain combined with terms for inci-
dence. Appendix A shows the full search strategy for MEDLINE and
AMED.

Cohort studies were included if they had the outcome of onset of
knee pain/OA, described symptomatically or radiographically. We
excluded caseecontrol studies as they are more prone to selection
bias and are often considered as delivering less reliable evidence6.
In our previous review, conclusions from cohort and caseecontrol
studies were generally consistent with each other but caseecontrol
studies gave larger effect sizes5. In the current review, studies were
included if the mean age of participants at follow-up was 50 or
above in order to ascertain risk factors that were relevant to older
adults. As in the previous review, risk factors assessed were de-
mographic, socio-economic, co-morbidity related and patient
determined, such as weight, age, gender and previous knee injury.
Studies that defined onset of knee problems in terms of total knee
replacement (TKR) or other surgical interventions were excluded,
as were the studies that treated such interventions as a risk factor
for onset of knee pain or OA. Surgery is usually the most definitive
intervention for severe OA and is unlikely to relate to the original
onset of knee pain/OA. Studies relating to inflammatory arthritis,

Fig. 1. Flow diagram for: Current evidence on risk factors for kne

such as rheumatoid arthritis, were also excluded as the patho-
physiological process involved is different to OA and therefore has
different risk factors. Appendix B shows full inclusion and exclusion
criteria. A flow chart of the study selection is shown in Fig. 1.

Two authors independently reviewed all identified abstracts,
with a third author reviewing those where a consensus had not
been reached. Two authors then assessed all remaining papers for
inclusion in the final review. Disagreements were resolved by
consensus.

Data extraction
Odds ratios (OR) for the association of each potential risk factor

with knee pain were extracted (or calculated where information
allowed) from each paper included in the final review. Symptom-
atic OA was usually diagnosed clinically using patient reported
symptoms of pain, stiffness or reduced function. Radiographic
based OA was based either on an increasing Kellgren Lawrence (K/
L) score or a K/L score of 2 or more.

Where more than one paper included data from the same study,
the results from the longest follow-up or the most recently pub-
lished paper were included. If studies presented both unadjusted

e OA in older adults: a systematic review and meta-analysis.

V. Silverwood et al. / Osteoarthritis and Cartilage 23 (2015) 507e515 509

ORs and ORs adjusted for potential confounders, adjusted ORs were
used.

Meta-analysis
Where risk factors had consistent definitions across studies and

effect estimates were reported in a similar fashion, meta-analyses
were conducted to obtain pooled estimates and associated 95%
confidence intervals (CI). The I2 statistic was calculated to assess the
proportion of total variance accounted for by heterogeneity be-
tween studies7. DerSimonian and Laird random effects models8

were then used to calculate the pooled OR as significant hetero-
geneity was present between studies for each risk factor.

For the purpose of this review, overweight was defined as a BMI
of 25e30 and obesity as a BMI over 30. If BMI was analysed on a
continuous scale, then unit effect sizes were converted to that per
five units to reflect comparison of an overweight BMI of 28 against a
normal BMI of 23, and also to per 10 units to allow comparison of an
obese BMI of 33 against a normal BMI.

Where possible results for people who currently smoked were
compared with those for people who never smoked. If this was not
possible, we compared people who had a previous smoking history
to those with none. If studies had assessed the effect of heaviness of
smoking, we used the estimated effect for light/moderate smoking
compared with no smoking.

The previous review4 showed that weighting studies by their
methodological quality did not alter the conclusions, or greatly
alter the pooled estimates; therefore we did not assess the meth-
odological quality of studies for this review.

Table I
Pooled ORs for association of commonly studied risk factors with knee OA

Risk factor No of
studies

Total no of
participants

Pooled
OR

Lower
CI

Upper
CI

I squared

Overweight 22 398,251 1.98 1.57 2.2 98.8
Obesity 22 401,119 2.66 2.15 3.28 98.7
Overweight

or obese
25 415,613 2.10 1.82 2.42 99.2

Previous knee
injury

13 27,326 2.83 1.91 4.19 89.1

Female gender 11 28,133 1.68 1.37 2.07 72.5
Hand OA 6 5232 1.30 0.90 1.87 54.7
Smoking 13 362,061 0.92 0.83 1.01 43.6

Phase 2 e Population attributable fractions (PAFs)

To illustrate the contribution of the main risk factors on knee
pain/OA, the second phase of the study mapped the pooled effect
size estimates for modifiable factors obtained in the meta-analyses
onto data collected from a previous cohort study to determine
PAFs for knee OA in the general population. PAFs allow estimation
of the proportion of new cases of knee pain/OA in the population
that could be avoided if the risk factor was removed, essentially
therefore the proportion of new cases related to the risk factor.

The Knee Pain Screening Tool (KNEST) study was a prospective
cohort study in North Staffordshire, UK. A baseline questionnaire
was sent to all patients aged 50 and over registered at three general
practices. Participants who responded to the baseline questionnaire
were also sent a 3 year questionnaire. The study was approved by
the North Staffordshire Local Research Ethics Committee.

Full details of the study have been given elsewhere. The ques-
tionnaire included the KNEST, a validated measure, which includes
a question on knee pain (whether the respondent has had pain in or
around the knee in the last year) and whether they have ever had a
knee injury which required consultation with a GP8,9.

Self-reported height and weight at baseline were used to
determine BMI.

Of the 8995 people sent a baseline questionnaire, 6792
(adjusted response 77%) responded. Of these 6792 subjects, 5784
were still registered at the practices at follow-up and hence sent a
follow-up questionnaire. 3907 (adjusted response 68%) responded
and answered the KNEST knee pain question at both baseline and
follow-up8,9.

PAFs for onset of knee OA at 3 years were determined using
logistic regression modelling10 among those KNEST participants
that reported no knee pain at baseline. The model was initially used
to calculate the probability of onset of knee OA for each KNEST
participant using their actual status (present or absent) on each risk
factor and applying as the regression coefficients the log of the

pooled odds ratio estimates for that risk factor obtained in the
meta-analysis.

The sum of these probabilities (N1) across participants equates
to the predicted level of onset of knee OA in the population based
on the actual prevalence of the risk factors in the KNEST population.
The model was then repeated with the risk factor of interest coded
as absent for all participants and the predicted number of cases
determined by again summing the participants’ probabilities (N2).
The PAF for each risk factor was then calculated as:
ðN1 � N2Þ=N1 � 100.

Stata 12.1 was used for all statistical analyses11.

Results

Phase 1 e Systematic review and meta-analysis

Study characteristics
6554 papers were identified using the search strategy. 6474

were excluded at title and abstract screening and 34 after reading
the papers in full. In total, 46 papers were included in this review
with 34 included in the meta-analysis.

Study results
Meta-analysis was performed for five risk factors where a suf-

ficient number of studies reported findings. These were: BMI,
where three pooled OR’s were calculated (overweight, obese,
overweight or obese), female gender, smoking, previous knee
injury and the presence of hand OA/Heberden’s nodes. Table I gives
the pooled OR’s obtained from the random effects meta-analyses.

Overweight
In total, 23 cohort studies in 23 papers reported on being

overweight12e34. The studies consistently demonstrated being
overweight was a risk factor for the onset of knee OA, though there
was considerable heterogeneity present among the results re-
ported (I2 ¼ 98.8%). The OR for being overweight as calculated from
one study18 was unusually high (OR 16.9, 95%CI 12.1e23.5), hence
was excluded from the meta-analysis. The pooled OR of the
remaining twenty-two studies was 1.98 (95% CI 1.57e2.20). One
study suggested that gain in weight was directly correlated with an
increasing risk of knee OA14. One study compared the risk of being
overweight on developing knee OA to that of developing hip OA and
found the association between being overweight and the devel-
opment of hip OA was weaker35.

Obesity
Twenty-three cohort studies investigated obesity as a risk factor

for onset of knee OA12e26,28e34,36. One of these studies18 was
excluded from the meta-analysis as the implied OR for obesity was
285. Among the remaining 22 studies, there was a large amount of
heterogeneity between the study findings (I2 ¼ 98.7%), however all

V. Silverwood et al. / Osteoarthritis and Cartilage 23 (2015) 507e515510

studies were generally consistent in reporting being obese as a risk
factor for the onset of knee OA. The pooled OR of the 22 studies was
2.66 (95% CI 2.15e3.28). This pooled estimate demonstrates that
obesity has a slightly larger effect on onset of knee OA than being
overweight.

Overweight OR obese
Twenty-six cohort studies reported results, or could have such

results deduced, on assessing the effect of being either overweight
or obese (BMI over 25)12e26,28e35,37e39. One such study18 was
excluded from the meta-analysis as the deduced OR for being
overweight or obese was 69. The I2 among the remaining twenty-
five studies was 99.2% and the resulting pooled OR was 2.10 (CI
1.82e2.42) showing an increased risk of knee OA in those over-
weight or obese (Fig. 2).

Previous knee injury
Thirteen cohort studies were included in the meta-analysis of

previous knee injury as a risk factor for the onset of knee
OA9,13e15,17,18,21,23,31,32,37,40,41 with only one showing that those with
previous knee injury had a lower, though non-significant risk of
developing knee OA14. The other studies all showed increased risk
of knee OA with a prior injury. The extent of heterogeneity present
between findings reported was considerable (I2 ¼ 89.1%) and the
pooled OR was 2.83 (95% CI 1.91e4.19) (Fig. 3).

Overall

Gelber (1999)

D’Souza (2008)

Toivanen (2010)

Cooper (2000)

Ingham (2011)

Muraki (2012)

McAlindon (1996)

Mork (2012)

Grotle (2008)
Reijman (2007)

Jinks (2006)

Seavey (2003)

Jarvholm (2005)
Hochberg (2004)

Hootman (2003)

Cheng (2000)

Zhang (2011)

Nishimura (2011)

Hart (1999)

Niu (2009)

Lachance (2002)

Manninen (1996)

Szoeke (2006)

Felson (1997)

Spector (1994)

Study

1.5 2

Fig. 2. Forest Plot of association of overweight or obese with

Female gender
Eleven cohort studies assessed female gender as a potential

risk factor9,12,14e16,21,23,24,26,31,34, (other studies used it as an
adjustment factor without reporting its effect estimates). One
paper did not include enough information to be included in the
meta-analysis32. There was consistent evidence that females were
at higher risk of knee OA. I2 was 72.5% and pooled OR was 1.68
(95% CI 1.37e 2.07).

Hand OA/Heberden’s nodes
Hand OA, usually diagnosed clinically by the presence of

Heberden’s nodes, was assessed as a risk factor by six cohort
studies14,17,24,34,37,42. The extent of heterogeneity was moderate and
on border of significance at the 5% level (I2 ¼ 54.7). The pooled OR
of 1.30 (95% CI 0.90e1.87) indicated that hand OA may potentially
be a risk factor for knee OA.

Smoking
Fourteen studies assessed smoking as a potential risk fac-

tor13,14,17,19,20,23,24,26,28,31,34,38,43,44. One was not included in the
meta-analysis as it measured smoking differently to the other pa-
pers44. The pooled OR of 0.92 (95% CI 0.83e1.01, I2 ¼ 43.6) suggests
that overall smoking is not associated with knee OA.

2.10 (1.82, 2.42)

3.30 (1.60, 6.81)

1.30 (1.26, 1.34)

2.52 (1.71, 3.71)

9.10 (2.60, 31.85)

1.45 (1.25, 1.68)

1.91 (1.69, 2.16)

4.10 (2.61, 6.44)

2.45 (2.00, 3.00)

2.20 (1.50, 3.23)
2.52 (1.80, 3.53)

1.14 (0.97, 1.34)

1.35 (1.07, 1.70)

3.39 (2.85, 4.03)
1.78 (1.51, 2.10)
1.78 (1.74, 1.82)

1.47 (1.06, 2.04)

1.64 (1.15, 2.34)
5.01 (4.60, 5.46)

2.01 (1.32, 3.06)

2.76 (1.78, 4.28)

1.44 (1.41, 1.47)

1.80 (1.70, 1.91)

2.94 (2.83, 3.05)

2.02 (1.65, 2.47)

4.69 (0.63, 34.91)

OR (95% CI)

4 8

knee OA. Pooled OR 2.10; 95% CI 1.82e2.42 I2 ¼ 98.9%.

Overall
Zhang (2011)
Cooper (2000)

Wilder (2002)

Toivanen (2010)
Study

Gelber (2000)

Ingham (2011)

Kujala (2000)

Hart (1999)
Muraki (2012)
Felson (1997)

Jinks (2008)

McAlindon (1996)
Hootman (2003)

2.83 (1.91, 4.19)

1.96 (0.98, 3.92)

4.80 (1.00, 23.04)

7.40 (5.90, 9.28)

5.10 (1.40, 18.58)

OR (95% CI)

5.01 (2.80, 8.96)

2.37 (1.98, 2.84)

4.73 (1.32, 16.95)

1.85 (0.82, 4.17)

2.91 (1.26, 6.72)

0.70 (0.10, 4.90)

1.59 (1.17, 2.16)

2.80 (1.40, 5.60)

1.80 (1.42, 2.28)

1.5 2 4 8

Fig. 3. Forest Plot of association of previous knee injury with knee OA. Pooled OR 2.83; 95% CI 1.91, 4.19 I2 ¼ 89.1%.

V. Silverwood et al. / Osteoarthritis and Cartilage 23 (2015) 507e515 511

Increasing age
Nineteen studies assessed increasing age as a risk factor for knee

OA9,12,13,15e17,19e21,23,24,26,28,31,32,34,38,45,46. Creating a pooled OR was
not possible as the studies used a range of different age catego-
risations. They were generally in agreement that increasing age was
a significant risk factor for onset of knee OA. Jarvholm et al. sug-
gested a ‘non-linear’ relationship between age and knee OA inci-
dence with a sharp increase in incidence between the ages of 50
and 75 in male patients but limited increase above age 7520.
Another study agreed with this and suggested that a ‘levelling off or
decline’ occurred after the age of 8046.

Occupational risks
Occupational activities were also discussed in several cohort

studies. Having a heavy physical workload was investigated by two
studies26,31, but both found it to be non-significant.

Kneeling was investigated by four studies18,21,32,34 and found to
be significantly related to knee OA by three18,21,32, suggesting that it
is an important element of physical work that can be classed as a
risk factor for knee pain and knee OA. Lifting was also assessed by
three studies21,32,34 and was significantly related to knee OA by
one32. One study assessed farming and construction work and
found that both were significant risk factors for knee OA47. One
study found a non-significant relationship of bending with knee
OA48. In summary, it would appear that individuals who are
exposed to certain physically demanding activities in their daily
working lives may be at an increased risk of developing knee pain
and knee OA.

Physical activity
High levels of physical activity were assessed by sixteen

studies13e15,17,18,22,26,31,34,37,38,45,49e52. Three papers showed a

statistically significant relationship between high levels of
physical activity or intense physical activity such as long-distance
running and the development of knee OA14,37,50. One study sug-
gested that it was habitual physical activity which created the
greatest risk meaning that those with more varied exercise rou-
tines had less risk of developing knee OA14 and another only
found an increased risk of developing knee OA in those who ran
20 miles or more each week38. All other papers discussed a
theoretical risk but did not demonstrate significant results.
Referring back to our inclusion criteria, we only looked at studies
discussing the general population so these results do not include
athletes or professional sportsmen. One study suggested that
higher levels of physical activity were associated with knee OA in
younger men (aged 20e49) but not in men older than 50 or in
women38.

Co-morbidities
Two studies26,36 concluded that cardiovascular disease such as

hypertension or ischaemic heart disease are risk factors and one of
those also suggested that respiratory illness could contribute36.
However Mork et al. suggest that a sedentary lifestyle exacerbated
by knee pain/OA could make such co-morbidities worse, hence a
dual association22 with the knee OA and the co-morbidity accel-
erating the progression of each other.

Depression was studied in three studies9,26,53 and two of these
found a statistically significant link with knee OA9,26. Experiencing
unspecified pain elsewhere in the body was also found to be sig-
nificant by two papers.9,21

Oestrogen
Four papers investigated the effect of oestrogen. Some sug-

gested that ingestion of oestrogen, predominantly in the form of

V. Silverwood et al. / Osteoarthritis and Cartilage 23 (2015) 507e515512

Hormone Replacement Therapy, may offer some protection against
knee OA17,28,32,51, and three papers proposed that patients who had
a hysterectomy, therefore had less endogenous oestrogen exposure,
were more likely to develop knee OA17,39,54. However, none of the
associations were statistically significant. Hart et al. presented
findings that current oestrogen use may play a protective effect
against women developing knee OA17.

Education and household income
Jorgensen et al. assessed level of education and their findings

suggest that even a basic education may be associated with reduced
risk of developing knee OA55 however, this is not supported by two
other studies that assessed education level9,26.

Three papers assessed whether having a higher household in-
come or a professional job is associated with a reduced risk of
developing knee OA9,17,55, with two reporting significant
results17,55.

Other
Several other risk factors were also discussed by a small number

of studies.
Poor self-evaluation of health9,53 was proposed as a potential

risk factor but statistically no association was demonstrated. There
was also no association found between alcohol use and knee pain23.
One study found that being hyper-mobile could be protective56.

One study found that those who had been married, divorced or
widowed were statistically more likely to have knee pain and knee
OA rather than those who were unmarried and that having children
was a statistically significant risk factor55. Another study consid-
ered the association of cohabiting status with knee OA but did not
demonstrate any statistical significance9.

Results phase 2 e PAFs

We calculated PAFs for being overweight or obese and having
previous knee injury as these were the two strongest modifiable
risk factors, had a pooled OR obtained from the meta-analysis, and
had available information in the KNEST study. Table II shows the list
of PAFs calculated.

The PAFs indicates that for an estimated 5.1% of new knee pain/
OA patients, this is related to a previous injury. An estimated 17.3%
of new cases of knee pain is related to obesity and 24.6% to being
overweight or obese.

Discussion

This systematic review aimed to provide up-dated evidence on
the risk factors for developing knee pain/OA among older adults.
The findings are timely due to the 2014 update to the NICE OA
guidelines for managing OA in adults57. Since the publication of our
last review (studies up to January 2008)5, there has been further
evidence to support the effect of previously known risk factors of
increased BMI, previous knee injury, age, being female and hand
OA. The conclusion that there is no association of smoking with
onset of knee OA remained when adding more recent literature.
Quantitative pooling of results was feasible for five risk factors; all

Table II
PAFs for overweight, obesity and previous knee injury for
onset of knee pain

Risk factor PAF

Injury 5.1%
Obesity 17.3%
Overweight or obese 24.6%

except smoking and Heberden’s nodes were found to have a sig-
nificant effect on development of knee OA. Individual study effect
size estimates for smoking tended to suggest there may be a
negative association with onset of knee OA, however only one such
study showed a significant relationship. The pooling of results
showed non-significant association.

The findings of this review together with NICE Osteoarthritis
guidelines (2014) emphasise the continued importance of weight
loss as a management option for OA57. Our calculated PAF values
demonstrate that 24.6% of cases of onset of knee pain could be
attributed to being either overweight or obese. According to the
National Joint Registry, 90,842 TKR’s took place in 2012, an increase
of 7.3% in number of procedures from 201158. Primary TKR plus 5
years of follow-up care is estimated to cost £7458 per patient59. This
means that the financial implications of severe knee OA are sig-
nificant for the National Health Service.

Health care professionals sometimes have difficulty in dis-
cussing weight issues with patients with OA60, a recent study
found that people with OA are still more likely to receive phar-
macological treatments than non pharmacological treatments
(including weight loss advice)61. A recent Cochrane review on the
effectiveness of interventions to change health care professionals
behaviour to promote weight reduction did not provide firm
conclusions62 leaving a gap in knowledge about how to address
this problem. The need for training to address barriers to health
professionals providing support and advice has previously been
highlighted63 and new approaches to support clinicians to
discuss weight loss strategies with patients are urgently required.
Finally, recent research adds to the complexity by highlighting
the interplay between pain, biomechanics and weight loss,
thereby requiring interventions to take account of multiple
factors64.

There is increasing but still low levels of evidence that certain
occupational activities such as kneeling, high levels of physical
activity, farming and construction work, and comorbid conditions
such as depression or cardiovascular disease are risk factors for
knee OA. High levels of physical activity appear to increase risk of
knee OA where patients undertake habitual and repetitive motion,
whereas in comparison those who undertake a less intense exercise
pattern do not appear to have increased risk. In comparison it can
be concluded that having a sedentary lifestyle increases the risk of
excess bodyweight and associated co-morbidities therefore a pa-
tients should try to vary their exercise and create an element of
balance between high-impact and repetitive motion and lower
impact exercise.

A limited number of studies investigating socio-economic status
such as household income or having a professional job found these
attributes to be protective of developing knee OA.

Case-control studies were excluded from this review. Including
them may have added to the evidence on certain risk factors but
they are generally regarded as representing a lower level of evi-
dence given particularly the potential of selection bias in choosing
controls. Our previous review suggested including caseecontrol
studies would not have altered our conclusions although case-
controls studies, unlike cohort studies, did suggest smoking had a
negative association with knee OA, and they also tended to give
increased strengths of associations. We did not assess quality of the
studies, again because in our previous review accounting for quality
of studies made no difference to our findings. We also excluded
non-English language papers as part of our exclusion criteria, which
means that potentially there could be additional studies which
were missed. We used the I2 statistic to calculate heterogeneity,
which was moderate for hand OA and high for all other risk factors
therefore despite using random effects meta-analysis some caution
is needed in interpreting the pooled ORs.

Searches Results

1 exp Osteoarthritis/
2 knee$1.mp.
3 1 and 2
4 (knee$ adj3 (osteoarthr$ or pain$ or disab$5)).mp.
5 3 or 4
6 incidence.sh. or exp mortality/or follow-up studies.sh. or

prognos$.tw. or predict$.tw. or course.tw.
7 risk$.tw.
8 6 or 7
8 5 and 8

Search 12/12/12.

V. Silverwood et al. / Osteoarthritis and Cartilage 23 (2015) 507e515 513

Given the size and scope of this review, it was not possible to
cover all potential risk factors for knee OA. For example, this sys-
tematic review does not consider risk factors such as low muscle
strength or mal-alignment.

In phase 2 of our study we could not calculate PAFs for hand OA
as this was not included in the KNEST study. The definition of knee
pain was self-reported and may not reflect radiographic OA but it is
likely that knee pain in the elderly is related to OA. Use of a larger
more comprehensive dataset would have been beneficial to
calculate impact numbers for these risk factors, and this may be
addressed in a different study. It is also important to note that there
are different ways of estimating PAFs, all of which may result in
slightly different estimates65. However the PAFs determined here
give an idea of how much of new knee pain may be related to
obesity, overweight and previous injury.

In conclusion, this review has identified several risk factors for
the development of knee pain and knee OA in older adults. The
results of this review can be used clinically to help healthcare
professionals identify and manage patients at risk of developing or
increasing knee OA. Some, such as weight, can be targeted clini-
cally in order to reduce the number of patients who suffer from
knee OA. Patients with other risk factors such as previous knee
injury, age and female gender can be managed to reduce pro-
gression of the condition. There is however limited evidence
regarding factors such as the influence of co-morbidities, and
socio-economic status and therefore further research needs to
focus on these risk factors rather than those for which extensive
evidence already exists.

Contributions

CJ, KJ, and MB conceived the study. VS, MB and JJ performed the
searches. VS, MB, CJ and KJ extracted the data. VS and MB per-
formed the analyses. All authors contributed to the interpretation
of the findings. VS drafted the paper and all authors critically
revised it and approved the final manuscript.

Funding
VS is an Academic Foundation Doctor whose post is funded by the
National Institute for Health Research (NIHR).

MB is funded by the NIHR School for Primary Care Research
(SPCR). This article presents independent research funded by the
NIHR. The views expressed are those of the author(s) and not
necessarily those of the NHS, the NIHR or the Department of Health.

The baseline KNEST survey was funded by The West Midlands
New Blood Research Fellowship Committee and the Haywood
Rheumatism Research and Development Foundation (HRRDF),
North Staffordshire, UK. The follow-up survey was funded by the
North Staffordshire Research and Development.

Consortium

The funders played no involvement in the study.

Competing interests
None.

Appendix A. Search Strategy for MEDLINE

Search Strategy.
Medline & AMED.
Prognosis search filter (maximise sensitivity) e http://hiru.

mcmaster.ca/hiru/HIRU_Hedges_MEDLINE_Strategies.aspx.

Appendix B. Inclusion and Exclusion Criteria

Inclusion Criteria.

� English language
� Quantitative studies: cohort studies
� Outcome of onset of knee OA, knee pain, knee disability or
physical limitations relating to knee or radiographic knee OA.

� Mean age at follow-up of 50þ or age stratified analysis with 50þ
strata

� Risk factors must be demographic, socio-economic, comorbid,
previous knee events (for example injury) and other patient
determined factors

� Primary care population

Exclusion Criteria.

� Knee pain related to other musculoskeletal conditions e.g.,
rheumatoid arthritis, rheumatism

� Studies whose outcome is a total knee replacement or studies of
patients following total knee replacements.

� Animal studies
� Clinical risk factors or outcome including proprioception, mus-
cle strength, joint alignment, cartilage loss

� Conference abstracts
� Not an original study (e.g., editorial or literature review)
� Not English language
� Caseecontrol or cross sectional studies
� Studies in those with previous trauma/injury without general
population comparator group

References

1. Woolf AD, Pfleger B. Burden of major musculoskeletal condi-
tions. Bull World Health Organ 2003;81(9):646e56.

2. Bedson J, Jordan K, Croft P. The prevalence and history of knee
osteoarthritis in general practice: a case-control study. Fam
Pract 2005 Feb;22(1):103e8.

3. 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. Ann Rheum Dis 2001 Feb;60(2):91e7.

4. Jordan KP, Joud A, Bergknut C, Croft P, Edwards JJ, Peat G, et al.
International comparisons of the consultation prevalence of
musculoskeletal conditions using population-based healthcare
data from England and Sweden. Ann Rheum Dis 2014
Jan;73(1):212e8.

5. Blagojevic M, Jinks C, Jeffery A, Jordan KP. Risk factors for onset of
osteoarthritis of the knee in older adults: a systematic review and
meta-analysis. Osteoarthritis Cartilage 2010 Jan;18(1):24e33.

6. Centre for Evidence Based Medicine. Available at: http://www.
cebm.net/index.aspx?o¼5653; 2013. Accessed 24/04, 2014.

http://hiru.mcmaster.ca/hiru/HIRU_Hedges_MEDLINE_Strategies.aspx

http://hiru.mcmaster.ca/hiru/HIRU_Hedges_MEDLINE_Strategies.aspx

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref1

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref1

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref1

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref2

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref2

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref2

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref2

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref3

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref3

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref3

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref3

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref4

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref4

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref4

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref4

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref4

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref4

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref5

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref5

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref5

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref5

http://www.cebm.net/index.aspx?o=5653

http://www.cebm.net/index.aspx?o=5653

http://www.cebm.net/index.aspx?o=5653

V. Silverwood et al. / Osteoarthritis and Cartilage 23 (2015) 507e515514

7. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring
inconsistency in meta-analyses. BMJ 2003 Sep 6;327(7414):
557e60.

8. Jinks C, Jordan K, Ong BN, Croft P. A brief screening tool for
knee pain in primary care (KNEST). 2. Results from a survey in
the general population aged 50 and over. Rheumatology (Ox-
ford) 2004 Jan;43(1):55e61.

9. Jinks C, Jordan KP, Blagojevic M, Croft P. Predictors of onset
and progression of knee pain in adults living in the commu-
nity. A prospective study. Rheumatology (Oxford) 2008
Mar;47(3):368e74.

10. Greenland S, Drescher K. Maximum likelihood estimation of
the attributable fraction from logistic models. Biometrics 1993
Sep;49(3):865e72.

11. StataCorp. Stata Statistical Software: Release 12. College Sta-
tion, TX: StataCorp LP; 2011.

12. Hochberg MC, Lethbridge-Cejku M, Tobin JD. Bone mineral
density and osteoarthritis: data from the Baltimore Longitu-
dinal Study of Aging. Osteoarthritis Cartilage 2004;12(Suppl
A):S45e8.

13. Hootman JM, Macera CA, Helmick CG, Blair SN. Influence of
physical activity-related joint stress on the risk of self-
reported hip/knee osteoarthritis: a new method to quantify
physical activity. Prev Med 2003 May;36(5):636e44.

14. Felson DT, Zhang Y, Hannan MT, Naimark A, Weissman B,
Aliabadi P, et al. Risk factors for incident radiographic knee
osteoarthritis in the elderly: the Framingham Study. Arthritis
Rheum 1997 Apr;40(4):728e33.

15. McAlindon T, Zhang Y, Hannan M, Naimark A, Weissman B,
Castelli W, et al. Are risk factors for patellofemoral and tibio-
femoral knee osteoarthritis different? J Rheumatol 1996
Feb;23(2):332e7.

16. Manninen P, Riihimaki H, Heliovaara M, Makela P. Overweight,
gender and knee osteoarthritis. Int J Obes Relat Metab Disord
1996 Jun;20(6):595e7.

17. Hart DJ, Doyle DV, Spector TD. Incidence and risk factors for
radiographic knee osteoarthritis in middle-aged women: the
Chingford Study. Arthritis Rheum 1999 Jan;42(1):17e24.

18. Kujala UM, Kettunen J, Paananen H, Aalto T, Battie MC,
Impivaara O, et al. Knee osteoarthritis in former runners,
soccer players, weight lifters, and shooters. Arthritis Rheum
1995 Apr;38(4):539e46.

19. Lachance L, Sowers MF, Jamadar D, Hochberg M. The natural
history of emergent osteoarthritis of the knee in women.
Osteoarthritis Cartilage 2002 Nov;10(11):849e54.

20. Jarvholm B, Lewold S, Malchau H, Vingard E. Age, bodyweight,
smoking habits and the risk of severe osteoarthritis in the hip
and knee in men. Eur J Epidemiol 2005;20(6):537e42.

21. Ingham SL, Zhang W, Doherty SA, McWilliams DF, Muir KR,
Doherty M. Incident knee pain in the Nottingham community:
a 12-year retrospective cohort study. Osteoarthritis Cartilage
2011 Jul;19(7):847e52.

22. Mork PJ, Holtermann A, Nilsen TI. Effect of body mass index
and physical exercise on risk of knee and hip osteoarthritis:
longitudinal data from the Norwegian HUNT Study.
J Epidemiol Community Health 2012 Aug;66(8):678e83.

23. Muraki S, Akune T, Oka H, Ishimoto Y, Nagata K, Yoshida M,
et al. Incidence and risk factors for radiographic knee osteo-
arthritis and knee pain in Japanese men and women: a lon-
gitudinal population-based cohort study. Arthritis Rheum
2012 May;64(5):1447e56.

24. Nishimura A, Hasegawa M, Kato K, Yamada T, Uchida A,
Sudo A. Risk factors for the incidence and progression of
radiographic osteoarthritis of the knee among Japanese. Int
Orthop 2011 Jun;35(6):839e43.

25. Niu J, Zhang YQ, Torner J, Nevitt M, Lewis CE, Aliabadi P, et al. Is
obesity a risk factor for progressive radiographic knee osteo-
arthritis? Arthritis Rheum 2009 Mar 15;61(3):329e35.

26. Seavey WG, Kurata JH, Cohen RD. Risk factors for incident self-
reported arthritis in a 20 year followup of the Alameda County
Study Cohort. J Rheumatol 2003 Oct;30(10):2103e11.

27. Shiozaki H, Koga Y, Omori G, Tamaki M. Obesity and osteoar-
thritis of the knee in women: results from the Matsudai Knee
Osteoarthritis survey. Knee 1999;6(3):189e92.

28. Szoeke CE, Cicuttini FM, Guthrie JR, Clark MS, Dennerstein L.
Factors affecting the prevalence of osteoarthritis in healthy
middle-aged women: data from the longitudinal Melbourne
Women’s Midlife Health Project. Bone 2006 Nov;39(5):
1149e55.

29. Jinks C, Jordan K, Croft P. Disabling knee paineanother
consequence of obesity: results from a prospective cohort
study. BMC Public Health 2006 Oct 19;6:258.

30. Grotle M, Hagen KB, Natvig B, Dahl FA, Kvien TK. Obesity and
osteoarthritis in knee, hip and/or hand: an epidemiological
study in the general population with 10 years follow-up. BMC
Musculoskelet Disord 2008 Oct 2;9:132. 2474-9-132.

31. Toivanen AT, Heliovaara M, Impivaara O, Arokoski JP, Knekt P,
Lauren H, et al. Obesity, physically demanding work and
traumatic knee injury are major risk factors for knee osteo-
arthritisea population-based study with a follow-up of 22
years. Rheumatology (Oxford) 2010 Feb;49(2):308e14.

32. Zhang W, McWilliams DF, Ingham SL, Doherty SA, Muthuri S,
Muir KR, et al. Nottingham knee osteoarthritis risk prediction
models. Ann Rheum Dis 2011 Sep;70(9):1599e604.

33. Reijman M, Pols HA, Bergink AP, Hazes JM, Belo JN,
Lievense AM, et al. Body mass index associated with onset and
progression of osteoarthritis of the knee but not of the hip: the
Rotterdam Study. Ann Rheum Dis 2007 Feb;66(2):158e62.

34. D’Souza JC, Werner RA, Keyserling WM, Gillespie B, Rabourn R,
Ulin S, et al. Analysis of the Third National Health and Nutri-
tion Examination Survey (NHANES III) using expert ratings of
job categories. Am J Ind Med 2008 Jan;51(1):37e46.

35. Gelber AC, Hochberg MC, Mead LA, Wang NY, Wigley FM,
Klag MJ. Body mass index in young men and the risk of subse-
quent knee and hip osteoarthritis. Am J Med 1999 Dec;107(6):
542e8.

36. Ettinger WH, Davis MA, Neuhaus JM, Mallon KP. Long-term
physical functioning in persons with knee osteoarthritis from
NHANES. I: effects of comorbid medical conditions. J Clin
Epidemiol 1994 Jul;47(7):809e15.

37. Cooper C, Snow S, McAlindon TE, Kellingray S, Stuart B,
Coggon D, et al. Risk factors for the incidence and progression
of radiographic knee osteoarthritis. Arthritis Rheum 2000
May;43(5):995e1000.

38. Cheng Y, Macera CA, Davis DR, Ainsworth BE, Troped PJ,
Blair SN. Physical activity and self-reported, physician-diag-
nosed osteoarthritis: is physical activity a risk factor? J Clin
Epidemiol 2000 Mar 1;53(3):315e22.

39. Spector TD, Hart DJ, Doyle DV. Incidence and progression of
osteoarthritis in women with unilateral knee disease in the
general population: the effect of obesity. Ann Rheum Dis 1994
Sep;53(9):565e8.

40. Wilder FV, Hall BJ, Barrett Jr JP, Lemrow NB. History of acute
knee injury and osteoarthritis of the knee: a prospective
epidemiological assessment. The Clearwater Osteoarthritis
Study. Osteoarthritis Cartilage 2002 Aug;10(8):611e6.

41. Gelber AC, Hochberg MC, Mead LA, Wang NY, Wigley FM,
Klag MJ. Joint injury in young adults and risk for subsequent
knee and hip osteoarthritis. Ann Intern Med 2000 Sep
5;133(5):321e8.

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref7

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref7

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref7

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref7

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref8

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref8

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref8

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref8

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref8

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref9

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref9

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref9

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref9

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref9

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref10

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref10

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref10

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref10

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref11

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref11

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref12

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref12

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref12

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref12

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref12

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref13

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref13

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref13

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref13

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref13

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref14

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref14

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref14

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref14

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref14

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref15

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref15

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref15

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref15

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref15

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref16

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref16

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref16

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref16

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref17

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref17

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref17

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref17

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref18

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref18

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref18

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref18

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref18

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref19

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref19

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref19

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref19

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref20

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref20

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref20

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref20

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref21

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref21

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref21

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref21

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref21

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref22

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref22

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref22

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref22

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref22

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref23

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref23

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref23

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref23

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref23

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref23

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref24

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref24

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref24

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref24

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref24

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref25

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref25

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref25

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref25

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref26

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref26

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref26

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref26

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref27

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref27

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref27

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref27

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref28

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref28

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref28

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref28

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref28

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref28

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref29

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref29

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref29

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref29

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref30

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref30

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref30

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref30

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref31

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref31

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref31

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref31

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref31

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref31

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref31

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref32

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref32

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref32

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref32

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref33

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref33

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref33

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref33

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref33

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref34

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref34

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref34

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref34

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref34

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref35

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref35

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref35

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref35

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref35

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref36

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref36

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref36

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref36

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref36

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref37

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref37

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref37

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref37

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref37

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref38

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref38

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref38

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref38

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref38

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref39

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref39

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref39

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref39

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref39

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref40

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref40

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref40

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref40

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref40

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref41

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref41

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref41

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref41

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref41

V. Silverwood et al. / Osteoarthritis and Cartilage 23 (2015) 507e515 515

42. Dahaghin S, Bierma-Zeinstra SM, Reijman M, Pols HA,
Hazes JM, Koes BW. Does hand osteoarthritis predict future
hip or knee osteoarthritis? Arthritis Rheum 2005 Nov;52(11):
3520e7.

43. Wilder FV, Hall BJ, Barrett JP. Smoking and osteoarthritis: is
there an association? The Clearwater Osteoarthritis Study.
Osteoarthritis Cartilage 2003 Jan;11(1):29e35.

44. Felson DT, Anderson JJ, Naimark A, Hannan MT, Kannel WB,
Meenan RF. Does smoking protect against osteoarthritis?
Arthritis Rheum 1989 Feb;32(2):166e72.

45. Felson DT, Anderson JJ, Naimark A, Walker AM, Meenan RF.
Obesity and knee osteoarthritis. The Framingham Study. Ann
Intern Med 1988 Jul 1;109(1):18e24.

46. Oliveria SA, Felson DT, Reed JI, Cirillo PA, Walker AM. Inci-
dence of symptomatic hand, hip, and knee osteoarthritis
among patients in a health maintenance organization. Arthritis
Rheum 1995 Aug;38(8):1134e41.

47. Vingard E, Alfredsson L, Goldie I, Hogstedt C. Occupation and
osteoarthrosis of the hip and knee: a register-based cohort
study. Int J Epidemiol 1991 Dec;20(4):1025e31.

48. Felson DT, Hannan MT, Naimark A, Berkeley J, Gordon G,
Wilson PW, et al. Occupational physical demands, knee
bending, and knee osteoarthritis: results from the Framing-
ham Study. J Rheumatol 1991 Oct;18(10):1587e92.

49. Deacon A, Bennell K, Kiss ZS, Crossley K, Brukner P. Osteoar-
thritis of the knee in retired, elite Australian Rules footballers.
Med J Aust 1997 Feb 17;166(4):187e90.

50. Verweij LM, van Schoor NM, Deeg DJ, Dekker J, Visser M.
Physical activity and incident clinical knee osteoarthritis in
older adults. Arthritis Rheum 2009 Feb 15;61(2):152e7.

51. Hannan MT, Felson DT, Anderson JJ, Naimark A. Habitual
physical activity is not associated with knee osteoarthritis: the
Framingham Study. J Rheumatol 1993 Apr;20(4):704e9.

52. Felson DT, Niu J, Clancy M, Sack B, Aliabadi P, Zhang Y. Effect of
recreational physical activities on the development of knee
osteoarthritis in older adults of different weights: the Fra-
mingham Study. Arthritis Rheum 2007 Feb 15;57(1):6e12.

53. Palmer KT, Reading I, Calnan M, Linaker C, Coggon D. Does
knee pain in the community behave like a regional pain syn-
drome? Prospective cohort study of incidence and persistence.
Ann Rheum Dis 2007 Sep;66(9):1190e4.

54. Samanta A, Jones A, Regan M, Wilson S, Doherty M. Is osteo-
arthritis in women affected by hormonal changes or smoking?
Br J Rheumatol 1993 May;32(5):366e70.

55. Jorgensen KT, Pedersen BV, Nielsen NM, Hansen AV,
Jacobsen S, Frisch M. Socio-demographic factors, reproductive
history and risk of osteoarthritis in a cohort of 4.6 million
Danish women and men. Osteoarthritis Cartilage 2011
Oct;19(10):1176e82.

56. Dolan AL, Hart DJ, Doyle DV, Grahame R, Spector TD. The
relationship of joint hypermobility, bone mineral density, and
osteoarthritis in the general population: the Chingford Study.
J Rheumatol 2003 Apr;30(4):799e803.

57. National Institute for Health and Clinical Excellence. NICE Clinical
Guideline 177. . In: Osteoarthritis: Care and Management in
Adults. Available at: http://www.nice.org.uk/nicemedia/live/
14383/66527/66527 ; 2014. Accessed 28/04, 2014.

58. National Joint Registry. National Joint Registry for England and
Wales. 10th Annual Report. http://www.njrcentre.org.uk/
njrcentre/Reports,PublicationsandMinutes/Annualreports/
tabid/86/Default.aspx. [Date accessed 04/03/2014].

59. Dakin H, Gray A, Fitzpatrick R, Maclennan G, Murray D, KAT
Trial Group. Rationing of total knee replacement: a cost-
effectiveness analysis on a large trial data set. BMJ Open
2012 Jan 30;2(1):e000332. 2011-000332. Print 2012.

60. Jinks C, Ong BN. ‘How would you go about that? I don’t know.’
A qualitative study on perceptions of prevention of knee pain
and disability. Eur J Public Health 2010;20. 171e171.

61. Healey EL, Afolabi EK, Lewis M, Edwards JJ, Jordan KP,
Finney A, Smith R, Jinks C, Dziedzic KS. Uptake of the NICE
osteoarthritis core treatments in community dwelling older
adults with a self-reported primary care consultation for joint
pain. Rheumatology 2014;53(1):i83. 2014 Abstracts.

62. Flodgren G, Parmelli E, Doumit G, Gattellari M, O’Brien M,
Grimshaw J, et al. Local Opinion Leaders: Effects on Profes-
sional Practice and Health Care Outcomes (Review). Available
at: http://apps.who.int/rhl/reviews/CD000125 ; 2011.
Accessed 28/04, 2014.

63. National Institute for Health and Clinical Excellence. NICE
Clinical Guideline 43. . In: Obesity: Guidance on the Preven-
tion, Identification, Assessment and Management of Over-
weight and Obesity in Adults and Children. Available at: http://
www.nice.org.uk/nicemedia/pdf/CG43NICEGuideline ;
2006. Accessed 24/04, 2014.

64. Abbate LM, Jordan JM. Weight change in osteoarthritis. Oste-
oarthritis Cartilage 2012 Apr;20(4):268e70.

65. Benichou J. A review of adjusted estimators of attributable risk.
Stat Methods Med Res 2001 Jun;10(3):195e216.

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref42

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref42

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref42

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref42

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref42

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref43

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref43

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref43

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref43

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref44

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref44

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref44

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref44

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref45

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref45

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref45

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref45

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref46

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref46

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref46

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref46

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref46

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref47

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref47

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref47

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref47

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref48

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref48

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref48

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref48

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref48

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref49

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref49

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref49

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref49

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref50

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref50

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref50

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref50

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref51

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref51

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref51

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref51

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref52

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref52

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref52

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref52

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref52

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref53

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref53

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref53

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref53

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref53

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref54

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref54

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref54

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref54

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref55

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref55

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref55

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref55

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref55

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref55

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref56

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref56

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref56

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref56

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref56

http://www.nice.org.uk/nicemedia/live/14383/66527/66527

http://www.nice.org.uk/nicemedia/live/14383/66527/66527

http://www.njrcentre.org.uk/njrcentre/Reports,PublicationsandMinutes/Annualreports/tabid/86/Default.aspx

http://www.njrcentre.org.uk/njrcentre/Reports,PublicationsandMinutes/Annualreports/tabid/86/Default.aspx

http://www.njrcentre.org.uk/njrcentre/Reports,PublicationsandMinutes/Annualreports/tabid/86/Default.aspx

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref58

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref58

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref58

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref58

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref59

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref59

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref59

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref59

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref60

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref60

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref60

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref60

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref60

http://apps.who.int/rhl/reviews/CD000125

http://www.nice.org.uk/nicemedia/pdf/CG43NICEGuideline

http://www.nice.org.uk/nicemedia/pdf/CG43NICEGuideline

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref63

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref63

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref63

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref64

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref64

http://refhub.elsevier.com/S1063-4584(14)01342-9/sref64

• Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis

Introduction
Methods
Phase 1 – Systematic review and meta-analysis
Search strategy and study selection
Data extraction
Meta-analysis
Phase 2 – Population attributable fractions (PAFs)
Results
Phase 1 – Systematic review and meta-analysis
Study characteristics
Study results
Overweight
Obesity
Overweight OR obese
Previous knee injury
Female gender
Hand OA/Heberden’s nodes
Smoking
Increasing age
Occupational risks
Physical activity
Co-morbidities
Oestrogen
Education and household income
Other
Results phase 2 – PAFs
Discussion
Contributions
Funding
Consortium
Competing interests
Appendix A. Search Strategy for MEDLINE
Appendix B. Inclusion and Exclusion Criteria
References