Knee Osteoarthritis: Muscle Weakness, Sensory Dysfunction and ... http://www.medscape.

org/viewarticle/733228_print

www.medscape.org

This article is a CME certified activity. To earn credit for this activity visit:
http://www.medscape.org/viewarticle/733228

CME Information
CME Released: 11/30/2010; Valid for credit through 11/30/2011

Target Audience

This activity is intended for primary care clinicians, rheumatologists, orthopaedists, and other health professionals caring for patients
at risk for knee OA.

Goal

The goal of this activity is to describe the risk factors for knee OA and suitable exercise interventions for at-risk patients.

Learning Objectives

Upon completion of this activity, participants will be able to:

1. Describe the association of muscle weakness with risk for knee OA

2. Describe the association of afferent sensory dysfunction with risk for knee OA
3. Describe suitable exercise training interventions for persons at risk for knee OA

Credits Available

Physicians - maximum of 0.50 AMA PRA Category 1 Credit(s)™

All other healthcare professionals completing continuing education credit for this activity will be issued a certificate of participation.

Physicians should only claim credit commensurate with the extent of their participation in the activity.

Accreditation Statements

For Physicians

This activity has been planned and implemented in accordance with the Essential Areas and policies of
the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape,
LLC and Nature Publishing Group. Medscape, LLC is accredited by the ACCME to provide continuing
medical education for physicians.

Medscape, LLC designates this educational activity for a maximum of 0.50 AM A PRA Category 1 Credit(s)™ . Physicians should
only claim credit commensurate with the extent of their participation in the activity.

Medscape, LLC staff have disclosed that they have no relevant financial relationships.

Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For
technical assistance, contact CME@medscape.net

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and
acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that
reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid
credit period that is noted on the title page.

1 จาก 12 20/1/2554 8:36

Knee Osteoarthritis: Muscle Weakness, Sensory Dysfunction and ... http://www.medscape.org/viewarticle/733228_print

Follow these steps to earn CME/CE credit*:

1. Read the target audience, learning objectives, and author disclosures.

2. Study the educational content online or printed out.
3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as
designated at the top of the test. MedscapeCME encourages you to complete the Activity Evaluation to provide feedback for
future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will
be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as
the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.

*The credit that you receive is based on your user profile.

Hardware/Software Requirements

MedscapeCME is accessible using the following browsers: Internet Explorer 6.x or higher, Firefox 2.x or higher, Safari 2.x or higher.
Certain educational activities may require additional software to view multimedia, presentation or printable versions of their content.
These activities will be marked as such and will provide links to the required software. That software may be: Macromedia Flash,
Adobe Acrobat, or Microsoft PowerPoint.

Authors and Disclosures

As an organization accredited by the ACCME, Medscape, LLC, requires everyone who is in a position to control the content of an
education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial
relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a
spouse or life partner, that could create a conflict of interest.

Medscape, LLC, encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and
Drug Administration, at first mention and where appropriate in the content.

Author(s)

Ewa M. Roos, PhD

Professor; Leader of the Multi-Professional Research Unit for Musculoskeletal Function and Physiotherapy, University of Southern
Denmark, Odense, Denmark

Disclosure: Ewa M. Roos, PhD, has disclosed no relevant financial relationships.

Walter Herzog, PhD

Director, Human Performance Lab, University of Calgary; Canada Research Chair; Killam Fellow for Molecular and Cellular
Biomechanics, Calgary, Alberta, Canada

Disclosure: Walter Herzog, PhD, has disclosed no relevant financial relationships.

Joel A. Block, MD

Willard L. Wood MD Chair in Rheumatology; Professor of Medicine, Rheumatology, and Biochemistry; Director, Section of
Rheumatology, Rush Medical College, Chicago, Illinois

2 จาก 12 20/1/2554 8:36

Knee Osteoarthritis: Muscle Weakness, Sensory Dysfunction and ... http://www.medscape.org/viewarticle/733228_print

Disclosure: Joel A. Block, MD, has disclosed no relevant financial relationships.

Kim L. Bennell, PhD

Professor; Director, Centre for Health, Exercise and Sports Medicine, Department of Physiotherapy, University of Melbourne,
Melbourne, Australia; Australian Research Council Future Fellow

Disclosure: Kim L. Bennell, PhD, has disclosed no relevant financial relationships.

Editor(s)

Jenny Buckland

Chief Editor, Nature Reviews Rheumatology

Disclosure: Jenny Buckland has disclosed no relevant financial relationships.

CME Author(s)

Laurie Barclay, MD

Freelance writer and reviewer, Medscape, LLC

Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

CME Reviewer(s)

Sarah Fleischman

CME Program Manager, Medscape, LLC

Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.

Laurie E. Scudder, DNP, NP

CME Accreditation Coordinator, Medscape, LLC

Disclosure: Laurie E. Scudder, DNP, NP, has disclosed no relevant financial relationships.

From Nature Reviews Rheumatology

CME
Ewa M. Roos, PhD; Walter Herzog, PhD; Joel A. Block, MD; Kim L. Bennell, PhD
CME Released: 11/30/2010; Valid for credit through 11/30/2011

Abstract and Introduction

Lower-extremity muscle strength and afferent sensory dysfunction, such as reduced proprioceptive acuity, are potentially modifiable
putative risk factors for knee osteoarthritis (OA). Findings from current studies suggest that muscle weakness is a predictor of knee
OA onset, while there is conflicting evidence regarding the role of muscle weakness in OA progression. In contrast, the literature
suggests a role for afferent sensory dysfunction in OA progression but not necessarily in OA onset. The few pilot exercise studies
performed in patients who are at risk of incident OA indicate a possibility for achieving preventive structure or load modifications. In
contrast, large randomized controlled trials of patients with established OA have failed to demonstrate beneficial effects of
strengthening exercises. Subgroups of individuals who are at increased risk of knee OA (such as those with previous knee injuries)
are easily identified, and may benefit from exercise interventions to prevent or delay OA onset.

3 จาก 12 20/1/2554 8:36

Knee Osteoarthritis: Muscle Weakness, Sensory Dysfunction and ... http://www.medscape.org/viewarticle/733228_print

Introduction

Patients with knee osteoarthritis (OA) seek medical care as a result of joint pain and functional loss. The structural hallmarks of OA
are cartilage loss (seen as joint-space narrowing on radiography) and bone changes (manifesting as osteophytes and subchondral
sclerosis). However, as cartilage is aneural, these structural changes are poorly related to the perceived joint pain. OA is also
associated with changes in other intra-articular and extra-articular joint structures, such as the synovium, menisci, ligaments, muscles
and the afferent sensory system. Research interest has increased into whether muscle function and the afferent sensory system are
risk factors for OA development and progression. Muscle function is more closely associated with joint pain than is joint-space
narrowing, and, as muscle function is easily modifiable, it is a potential therapeutic target in patients with this disease.

Muscles are critical for maintaining joint mobility, stability and function,[1] as they aid in shock absorption and proper force transfer
across the joint2 and provide dynamic stability to the normal and injured joint.[3-5] Muscle weakness has been associated with OA
onset and progression[6,7] by adversely affecting the ability to control joint movements accurately.[2,8] Muscle weakness is thought to
be one of the earliest and most frequent findings in patients with OA,[7] and is a better predictor of disability than either joint space
narrowing or pain.[7,9] While obesity, age, sex and joint injury have all been shown to be significant risk factors for OA,[10] the precise
nature by which they contribute to joint-degenerative changes remains speculative. Muscle weakness might be a unifying feature
explaining these risk factors (Figure 1), as muscle strength is lower in women than in men, is reduced following injury, decreases
with age and is lower relative to overall body mass in obese individuals.[11,12] However, while muscle weakness and atrophy
accompany OA,[13,14] it is not clear whether this weakness is caused by OA or precedes it, and, thus, whether it represents an
independent risk factor for disease onset and rate of progression. In this Review, we describe the roles of muscle weakness,
afferent sensory dysfunction and exercise in the development and progression of knee OA.

Figure 1. Joint Injury, Obesity, Age and Sex are Associated With Muscle Weakness and Afferent Sensory Dysfunction.
Addressing muscle weakness and afferent sensory dysfunction with strength and neuromuscular training in patients either at
risk of or with knee OA can be evaluated using various techniques for assessing structural outcomes. Abbreviation: OA,
osteoarthritis.

Muscle Weakness

Relevance of Animal Models to Human OA

4 จาก 12 20/1/2554 8:36

Knee Osteoarthritis: Muscle Weakness, Sensory Dysfunction and ... http://www.medscape.org/viewarticle/733228_print

Muscle weakness is easily studied in animal models of knee OA. Anterior cruciate ligament (ACL) transection is a frequently used
method to induce post-traumatic OA in a variety of animals. Following ACL loss, the quadriceps muscles atrophy and become
weaker.[15] In addition, forces across the knee are reduced during locomotion,[3] quadriceps activation is interrupted during stance
rather than being continuous (as found in the intact joint),[3] and hamstring muscles are activated at paw contact to prevent anterior
sliding of the tibia relative to the femur in cats,[3 as has also been observed in ACL-deficient dogs and humans.[16] Consequently,
load transfer across the joint is altered following ACL loss, and the associated instability of the knee, the loss of smooth control of
agonist and antagonist muscle interaction and the subsequent atrophy of the quadriceps muscles are thought to accelerate
degeneration of the joint.[1,17]

In an effort to study the effects of controlled muscle weakness on OA onset, Longino et al.[18] developed an animal model in which
quadriceps strength was reduced through injections of botulinum toxin A into the musculature. This technique induced muscle
weakness and atrophy, while locomotion remained relatively unaffected.[19] After 4 weeks of muscle weakness, retropatellar
cartilage degeneration, as evaluated histologically, was greater in the experimental rabbits compared to control rabbits, while the
tibiofemoral joint cartilage remained unaffected.[20] These results suggest that quadriceps weakness is an independent risk factor
for the onset of OA in the patellofemoral but not the tibiofemoral joints in rabbits.

The role of muscle weakness in OA onset and progression is less established in humans, as direct interventions to control muscle
weakness are difficult to perform. However, as observed in animal models, ACL loss in humans is associated with muscle
inhibition[21] and atrophy,[22] changes in activation patterns and gait kinematics,[23] and an increased risk of OA onset and
progression.[24] Furthermore, observational evidence links muscle weakness to increased radiographic joint disease and pain,[7,9]
and to an increased rate of OA development in elderly community-dwelling women.[25] Decreased isokinetic quadriceps strength in
women has also been found to be indicative of an increased rate of lower limb loading during locomotion,[2] and prolonged,
repetitive rapid loading of joints has been associated with both the initiation and progression of OA.[26,27] Although observational,
these studies support evidence obtained in animal models suggesting that muscle weakness is an independent risk factor for OA
and might provide a link between other risk factors such as age, sex, obesity and joint injury.

An Additional Risk Factor for Knee OA

Muscle weakness may be an important additional risk factor in groups of individuals who have a propensity for knee OA
development and progression. Obesity is a well characterized risk factor for the onset of knee OA,[10] and has been associated with
alterations in mechanical loading of the knee.[28] Furthermore, overweight individuals have a decreased percentage of lean body
mass, and thus reduced muscle strength relative to body size. Knee malalignment also increases knee load during walking (Figure
2a),[29] and can mediate the effects of other risk factors such as obesity.[30] While there is considerable evidence to support an
increased risk of OA progression in those with knee malalignment,[31,32] the relationship between malalignment and OA onset is
less clear and has given rise to contradictory findings.[33-36]

Figure 2. The Effects of Knee Malalignment on Knee Loading. a | Knee alignment can be categorized as genu valgum
(knock-knee), normal or genu varum (bow legged). A knock-knee will transfer more load to the outer compartment and a bow
knee will transfer more load to the inner compartment. b | Knee adduction moment represents the tendency to apply a varus

5 จาก 12 20/1/2554 8:36

Knee Osteoarthritis: Muscle Weakness, Sensory Dysfunction and ... http://www.medscape.org/viewarticle/733228_print

torque on the knee, forcing the knee laterally and compressing the medial compartment during the stance phase of walking. It
is created because the ground reaction force vector passes medial to the knee joint centre. The higher the adduction moment,
the greater the load on the medial compartment.

Neuromuscular Training

Patients who have experienced previous knee injury have an increased risk of developing OA. Up to 50% of all people with an ACL
injury—either isolated or combined with meniscal injury, with or without surgical reconstruction, or patients having meniscal surgery
only— develop OA within 10-15 years.[37,38] Muscle function is rarely fully restored in ACL-deficient patients, regardless of whether
they undergo surgical reconstruction,[39,40] and so is considered a potential contributor to OA development. An exception to this
trend is described in a prospective cohort study of 100 ACL-deficient patients who were treated using supervised neuromuscular
training and activity level modification.[41] Neuromuscular training programs aim to improve sensorimotor control and achieve
compensatory functional stability. Functional, weight-bearing exercises are designed to resemble conditions of daily life, with some
more-strenuous activities also included. The main emphases are on the knee-over-foot position and the quality of the patient's
performance in each exercise, with the level and progression of training intensity guided by the patient's neuromuscular function.[42]
The patients in this study showed a remarkably low rate of OA onset (16%) and few meniscal injuries after 15 years' follow-up.[24]
They also displayed good muscle function at 3 and 15 years, with the injured leg performing at 95-103% of the capacity of the
non-injured contralateral leg in tests of functional performance and isometric strength.[41] Strong muscles and good neuromuscular
function may be more relevant in ACL-deficient and meniscectomized individuals compared to those with normal knees, as
increased muscle strength and neuromuscular control is needed to absorb the altered knee load seen is patients with these defects.
[43,44]

Muscle Strengthening and Exercise Training

Protective Effects Against Onset of Knee OA. Evidence suggests that quadriceps weakness precedes the onset of knee OA,
thereby increasing the risk of disease development—possibly to a greater extent in women than in men.[25,45,46] The first
longitudinal study to investigate this connection, performed over a decade ago, found lower baseline quadriceps strength in women
who developed incident radiographic knee OA than in those who did not.[25] The most recent cohort study, which included over
2,000 individuals, showed that greater knee extensor strength protected against development of incident symptomatic knee OA in
both sexes.[46]

The implication of these longitudinal results is that lower-limb strengthening, particularly of the quadriceps, may be an effective
strategy to help prevent knee OA. Strength training programs usually involve non-weight-bearing exercises, which selectively train
isolated muscles. Weight-bearing exercises, which involve multiple joints, are also sometimes used. The emphasis is on the quantity
of muscle output, and the level of training and progression is guided by the patient's one-repetition maximum.[47] To date, the
effects of lower-limb strengthening on OA onset have only been investigated in one clinical trial.[48] A protective effect of
strengthening on radiographic disease onset was not demonstrated; however, adherence was low, the drop-out rate was high and
even the trained group lost lower-extremity muscle strength over the 30-month experimental period. Further studies are needed to
clarify the effects of increased muscle strength on OA onset.

Radiographic changes associated with OA onset and progression take years to develop, which makes this a problematic outcome
measure in exercise studies. Pilot studies using medial-compartment knee loading and cartilage glycosaminoglycan content as
proxies for structural modification in at-risk knees and in early disease have shown positive effects of exercise on joint health, and
might represent more-feasible study end points.[49-51]

4 months of physiotherapist-supervised neuromuscular training has been shown to increase glycosaminoglycan content in the
weight-bearing cartilage of the medial knee compartment in middle-aged meniscectomized patients, indicating that neuromuscular
training may have a role in preventing deleterious structural modifications of cartilage in this group of high-risk individuals.[50] Patients
in this study showed improved performance in functional tasks that require sensorimotor control, but did not improve quadriceps
strength or aerobic capacity,[52] lending further support to the importance of the neuromuscular component of the training program.

Protective Effects Against OA Progression? The relationship between quadriceps muscle strength and structural disease
progression in those with established knee OA is currently controversial. Two longitudinal cohort studies failed to find a significant
relationship between quadriceps strength and cartilage loss at the tibiofemoral joint,[53,54] while a controversial finding of increased
risk of disease progression in those with greater quadriceps strength and malaligned or lax knees [55] could not be replicated.[53]
Increased quadriceps strength might protect against cartilage degeneration in the lateral aspect of the patellofemoral
compartment,[53] suggesting that strength effects may depend upon the knee compartment involved.

Whether quadriceps-strengthening exercise could be a disease-modifying intervention is unclear, and further long-term studies are

6 จาก 12 20/1/2554 8:36

Knee Osteoarthritis: Muscle Weakness, Sensory Dysfunction and ... http://www.medscape.org/viewarticle/733228_print

needed before recommendations can be made. In a randomized controlled trial, the effects of a 12-week quadriceps-strengthening
program were compared in patients with medial knee OA with or without varus malalignment.[56] Despite strength increases in both
patient groups, quadriceps strengthening did not significantly alter the knee adduction moment during walking—an indicator of
medial knee load[57] and, importantly, a biomechanical factor that is thought to predict disease progression (Figure 2b).[58] In the
limited number of published clinical trials that directly measured joint structure,[48,59,60] there was no significant effect of lower-limb
strengthening on radiographic OA progression; however, a trend towards a beneficial effect was noted in the only study where
disease progression was the primary outcome.[48]

While the emphasis in the studies described above has been on quadriceps muscle strength, findings from a longitudinal cohort
study by Chang et at.[61] introduced the premise that the hip abductors might influence knee OA disease progression. Participants
with a lower hip adduction moment during walking (presumed to indicate hip abductor weakness) demonstrated more-rapid knee OA
progression. Patients with knee OA seem to have substantial weakness of the hip muscles,[62] but a large clinical trial published in
2010 did not support a role for hip-muscle strengthening in providing structural benefits.[63] A 12-week hip abductor strength
program was associated with significant increases in hip muscle strength but no change in hip adduction and knee adduction
moments during walking.[63] While hip-muscle strengthening may not be beneficial for slowing progression of well-established
disease, it has been shown to relieve pain and improve function in patients with knee OA.[51,63,64] For symptomatic benefits, then, it
seems the emphasis should be on strength training of the whole lower extremity and not only the quadriceps.

Afferent Somatosensory Dysfunction

Symptomatic OA is preceded by a prolonged sub-clinical phase. As OA onset and progression are mediated by aberrant
biomechanical joint loading,[65] subtle biomechanical aberrations that persist for years or decades may have important structural
consequences. The maintenance of efficient responses to forces generated during normal activity requires both intact
somatosensory afferents and functional musculoskeletal effectors. The afferent system includes pain, temperature, soft touch,
proprioception and vibration, among others (Figure 3). Proprioception is a complex sensation derived from multiple inputs that
provide the conscious and subconscious perception of position and motion in space, and includes the perception of joint position
and movement, muscle force, stretching and body position, as well as the unconscious regulation of postural response to positional
perturbations. Aside from visual, vestibular and auditory inputs, proprioception depends on afferent receptors in the muscles,
ligaments, synovial capsule and skin.[66,67]

Figure 3. The afferent somatosensory system comprises the receptors, afferent neurons and central processing centers that
permit the detection of a diverse range of environmental sensory inputs, including the tactile sense (touch), proprioception,
temperature and nociception (pain). Proprioception, including the sense of position in space, underlies the ability to maintain
erect posture, control joint movements and respond to perturbations. Hence, subtle dysfunction of the somatosensory afferent
system may alter dynamic loading of joints and alter the ability to protect joint tissue during motion.

Role of Proprioception in OA

As with the assessment of any aspect of the somato-sensory system, testing of proprioceptive acuity may focus on any of its
multiple inputs, and at various levels in the nervous system. However, in musculoskeletal diseases, joint position sense, assessed

7 จาก 12 20/1/2554 8:36

Knee Osteoarthritis: Muscle Weakness, Sensory Dysfunction and ... http://www.medscape.org/viewarticle/733228_print

by the ability to reproduce knee flexion to fixed angles, and the threshold of perception of passive motion are most commonly
assessed.[68] Using these techniques, it has been established that proprioceptive acuity declines with normal aging,[69,70] and that
patients with knee OA have significantly worse proprioceptive capacities than age-matched, normal individuals.[68,70,71] Moreover,
evaluation of the canine ACL transection model of OA has demonstrated that afferent denervation, either at the dorsal root ganglion
or the ipsilateral peripheral nerves, dramatically accelerates the development of OA.[72,73] Interestingly, the model is dependent on
joint destabilization, as denervation without ligament transection does not induce degenerative changes.[72,73] These observations,
in addition to the role that afferent innervation has in normal ambulation and posture, suggest that somatosensory dysfunction,
especially proprioceptive acuity, may be pathophysiologically important in OA.

Proprioceptive Acuity in OA Onset and Progression

The difficulty of determining whether proprioception has a potential role in OA pathophysiology—despite the clearly reduced
proprioceptive acuity among OA patients—is that, as noted above, proprioceptive acuity also declines with normal aging,[69,70] and
aging is the most important risk factor for developing OA. Moreover, the relationship between proprioception and OA pain is
complex: early cross-sectional observational studies failed to demonstrate an association,[74,75] but more-recent prospective,
longitudinal evaluations found significant, though modest, relationships between baseline proprioceptive acuity and the trajectory of
pain over time[76] and between improved proprioceptive acuity and pain palliation with exercise intervention.[77] Felson et al.[76]
confirmed the association between proprioceptive deficits (assessed by reproduction of knee flexion position) and knee pain, but
failed to identify a significant association with incident knee OA during 3 years of follow-up. Despite the short study duration relative
to the years of subclinical degeneration that often predate clinical OA, these findings do not support a clinically significant role for
proprioceptive deficits in the development of human OA.[78]

Important somatosensory deficits may be undetectable by conventional methodologies, as the high measurement errors yield large
minimal detectable differences among OA patients.[79] Also, perceived pain, adherence to study protocol and distraction can
confound results. Alternative testing strategies with improved precision, such as vibratory perception threshold (vPT), permit
detection of subtle yet potentially important somato-sensory deficits. Proprioceptive and vibratory pathways are co-localized in the
dorsal columns,[80] but vPT assessment is not confounded by pain, mobility or strict subject attention,[81] suggesting that vPT is a
preferable readout to conventional proprioceptive measurements. Reports have confirmed the presence of significant vPT deficits
in patients with knee OA, similar to the observed deficits in proprioception;[81] however, unlike proprioception, VPT can be tested
throughout the body, and vibratory deficits have also been reported in patients with hip OA, thus implicating somatosensory deficits
as a more general component of the lower extremity OA phenotype. Furthermore, studies have shown diminished VPT in the hands
of patients with hip or knee OA[78] and impaired proprioception at the elbows in patients with knee OA,[82] suggesting that the
somatosensory dysfunction underlying lower extremity OA is systemic rather than local.

Conclusions

Findings from current studies suggest that muscle weakness is a predictor of knee OA onset, while evidence regarding the role of
muscle weakness in OA progression is conflicting. In contrast, the literature suggests a role for afferent sensory dysfunction in OA
progression but not necessarily in OA onset. The small number of published exercise studies involving structural or load
modification outcomes suggest that neuromuscular exercise may be beneficial, especially in patients who are already at risk of OA
or in those with early disease. Subgroups at increased risk of knee OA, including patients with prior knee injury, are easily identified
and may benefit from exercise interventions to delay OA onset.

Key Points

Muscle weakness is a predictor of knee osteoarthritis onset

Afferent sensory dysfunction is a predictor of osteoarthritis progression
Exercise training interventions should address both muscle weakness and afferent sensory dysfunction
Exercise regimens that aim to achieve modification of joint loading or cartilage structure seem to be more promising in at-risk
individuals or those with early disease

This article is a CME certified activity. To earn credit for this activity visit:
http://www.medscape.org/viewarticle/733228

References

1. Brandt, K. D. Putting some muscle into osteoarthritis. Ann. Intern. Med. 127, 154-156 (1997) .

8 จาก 12 20/1/2554 8:36

Knee Osteoarthritis: Muscle Weakness, Sensory Dysfunction and ... http://www.medscape.org/viewarticle/733228_print

2. Mikesky, A. E., Meyer, A. & Thompson, K. L. Relationship between quadriceps strength and rate of loading during gait in
women. J. Orthop. Res. 18, 171-175 (2000).
3. Hasler, E. M., Herzog, W., Leonard, T. R., Stano, A. & Nguyen, H. In vivo knee joint loading and kinematics before and after
ACL transection in an animal model. J. Biomech. 31, 253-262 (1998) .
4. Herzog, W. et al. Material and functional properties of articular cartilage and patellofemoral contact mechanics in an
experimental model of osteoarthritis. J. Biomech. 31, 1137-1145 (1998).
5. Johansson, H., Sjölander, P & Sojka, P A sensory role for the cruciate ligaments. Clin. Orthop. Relat. Res. 268, 161-178
(1991).
6. Segal, N. A. et al. Quadriceps weakness predicts risk for knee joint space narrowing in women in the MOST cohort.
Osteoarthritis Cartilage 18, 769-775 (2010).
7. Palmieri-Smith, R. M., Thomas, A. C., Karvonen-Gutierrez, C. & Sowers, M. F. Isometric quadriceps strength in women with
mild, moderate, and severe knee osteoarthritis. Am. J. Phys. Med. Rehabil. 89, 541-548 (2010).
8. Radin, E. L. & Paul, I. L. Does cartilage compliance reduce skeletal impact loads? The relative force-attenuating properties
of articular cartilage, synovial fluid, periarticular soft tissue and bone. Arthritis Rheum. 13, 139-144 (1970).
9. McAlindon, T. E., Cooper, C., Kirwan, J. R. & Dieppe, P A. Determinants of disability in osteoarthritis of the knee. Ann.
Rheum. Dis. 52, 258-262 (1993).
10. Blagojevic, M., Jinks, C., Jeffery, A. & Jordan, K. P Risk factors for onset of osteoarthritis of the knee in older adults: a
systematic review and meta-analysis. Osteoarthritis Cartilage 18, 24-33 (2010).
11. Janssen, I., Heymsfield, S. B., Wang, Z. M. & Ross, R. Skeletal muscle mass and distribution in 468 men and women aged
18-88 yr. J. Appl. Physiol. 89, 81-88 (2000).
12. Lindle, R. S. et al. Age and gender comparisons of muscle strength in 654 women and men aged 20-93 yr. J.Appl. Physiol.
83, 1581-1587 (1997).
13. Lewek, M. D., Rudolph, K. S. & Snyder-Mackler, L. Quadriceps femoris muscle weakness and activation failure in patients
with symptomatic knee osteoarthritis. J. Orthop. Res. 22, 110-115 (2004).
14. Hurley, M. V., Scott, D. L., Rees, J. & Newham, D. J. Sensorimotor changes and functional performance in patients with knee
osteoarthritis. Ann. Rheum. Dis. 56, 641-648 (1997).
15. Herzog, W., Adams, M. E., Matyas, J. R. & Brooks, J. G. Hindlimb loading, morphology and biochemistry of articular cartilage
in the ACL-deficient cat knee. Osteoarthritis Cartilage 1, 243-251 (1993).
16. Brandt, K. D. et al. Anterior (cranial) cruciate ligament transection in the dog: a bona fide model of osteoarthritis, not merely of
cartilage injury and repair. J. Rheumatol. 18, 436-446 (1991).
17. Herzog, W. & Longino, D. The role of muscles in joint degeneration and osteoarthritis. J. Biomech. 40 (Suppl. 1), S54-S63
(2007).
18. Longino, D. Botulinum Toxin and a New Animal Model of Muscle Weakness. Thesis, University of Calgary (2003).
19. Longino, D., Frank, C. & Herzog, W. Acute botulinum toxin-induced muscle weakness in the anterior cruciate ligament-
deficient rabbit. J. Orthop. Res. 23, 1404-1410 (2005).
20. Rehan Youssef, A., Longino, D., Seerattan, R., Leonard, T. & Herzog, W. Muscle weakness causes joint degeneration in
rabbits. Osteoarthritis Cartilage 17, 1228-1235 (2009).
21. Suter, E. & Herzog, W. Does muscle inhibition after knee injury increase the risk of osteoarthritis? Exerc. Sport Sci. Rev. 28,
15-18 (2000) .
22. Snyder-Mackler, L., Binder-Macleod, S. A. & Williams, P R. Fatigability of human quadriceps femoris muscle following
anterior cruciate ligament reconstruction. Med. Sci. Sports Exerc. 25, 783-789 (1993).
23. Berchuck, M., Andriacchi, T. P, Bach, B. R. & Reider, B. Gait adaptations by patients who have a deficient anterior cruciate
ligament. J. Bone Joint Surg. Am. 72, 871-877 (1990).
24. Neuman, P et al. Prevalence of tibiofemoral osteoarthritis 15 years after nonoperative treatment of anterior cruciate ligament
injury: a prospective cohort study. Am. J. Sports Med. 36, 1717-1725 (2008).
25. Slemenda, C. et al. Reduced quadriceps strength relative to body weight: a risk factor for knee osteoarthritis in women?
Arthritis Rheum. 41, 1951-1959 (1998).
26. Radin, E. L., Orr, R. B., Kelman, J. L., Paul, I. L. & Rose, R. M. Effect of prolonged walking on concrete on the knees of
sheep. J. Biomech. 15, 487-492 (1982).
27. Simon, S. R., Radin, E. L., Paul, I. L. & Rose, R. M. The response of joints to impact loading. II. In vivo behavior of
subchondral bone. J. Biomech. 5, 267-272 (1972).
28. Andriacchi, T. P. & Mundermann, A. The role of ambulatory mechanics in the initiation and progression of knee osteoarthritis.
Curr. Opin. Rheumatol. 18, 514-518 (2006).
29. Sharma, L. et al. Knee adduction moment, serum hyaluronan level, and disease severity in medial tibiofemoral osteoarthritis.
Arthritis Rheum. 41, 1233-1240 (1998).

9 จาก 12 20/1/2554 8:36

Knee Osteoarthritis: Muscle Weakness, Sensory Dysfunction and ... http://www.medscape.org/viewarticle/733228_print

30. Felson, D. T., Goggins, J., Niu, J., Zhang, Y. & Hunter, D. J. The effect of body weight on progression of knee osteoarthritis
is dependent on alignment. Arthritis Rheum. 50, 3904-3909 (2004).
31. Cicuttini, F., Wluka, A., Hankin, J. & Wang, Y Longitudinal study of the relationship between knee angle and tibiofemoral
cartilage volume in subjects with knee osteoarthritis. Rheumatology (Oxford) 43, 321-324 (2004).
32. Sharma, L. et al. The role of knee alignment in disease progression and functional decline in knee osteoarthritis. JAMA 286,
188-195 (2001) .
33. Chang, A. et al. Frequency of varus and valgus thrust and factors associated with thrust presence in persons with or at higher
risk of developing knee osteoarthritis. Arthritis Rheum. 62, 1403-1411 (2010).
34. Brouwer, G. M. et al. Association between valgus and varus alignment and the development and progression of radiographic
osteoarthritis of the knee. Arthritis Rheum. 56, 1204-1211 (2007).
35. Hunter, D. J. et al. Knee alignment does not predict incident osteoarthritis: the Framingham osteoarthritis study. Arthritis
Rheum. 56, 1212-1218 (2007).
36. Sharma, L. et al. Varus and valgus alignment and incident and progressive knee osteoarthritis. Ann. Rheum. Dis. 69,
1940-1945 (2010).
37. Lohmander, L. S., Englund, P M., Dahl, L. L. & Roos, E. M. The long-term consequence of anterior cruciate ligament and
meniscus injuries: osteoarthritis. Am. J. Sports Med. 35, 1756-1769 (2007).
38. Oiestad, B. E., Engebretsen, L., Storheim, K. & Risberg, M. A. Knee osteoarthritis after anterior cruciate ligament injury: a
systematic review. Am. J. Sports Med. 37, 1434-1443 (2009).
39. Roos, E. M. Joint injury causes knee osteoarthritis in young adults. Curr. Opin. Rheumatol. 17, 195-200 (2005).
40. Ageberg, E., Thomee, R., Neeter, C., Silbernagel, K. G. & Roos, E. M. Muscle strength and functional performance in
patients with anterior cruciate ligament injury treated with training and surgical reconstruction or training only: a two to five-year
followup. Arthritis Rheum. 59, 1773-1779 (2008).
41. Ageberg, E., Pettersson, A. & Friden, T. 15-year follow-up of neuromuscular function in patients with unilateral
nonreconstructed anterior cruciate ligament injury initially treated with rehabilitation and activity modification: a longitudinal
prospective study. Am. J. Sports Med. 35, 2109-2117 (2007).
42. Ageberg, E. Consequences of a ligament injury on neuromuscular function and relevance to rehabilitation—using the anterior
cruciate ligament-injured knee as model. J. Electromyogr. Kinesiol. 12, 205-212 (2002).
43. Sturnieks, D. L. et al. Knee strength and knee adduction moments following arthroscopic partial meniscectomy. Med. Sci.
Sports Exerc. 40, 991-997 (2008).
44. Butler, R. J., Minick, K. I., Ferber, R. & Underwood, F. Gait mechanics after ACL reconstruction: implications for the early
onset of knee osteoarthritis. Br. J. Sports Med. 43, 366-370 (2009).
45. Hootman, J., Fitzgerald, S., Macera, C. & Blair, S. Lower extremity muscle strength and risk of self-reported hip or knee
osteoarthritis. J. Phys. Act. Health 1, 321-330 (2004).
46. Segal, N. A. et al. Effect of thigh strength on incident radiographic and symptomatic knee osteoarthritis in a longitudinal
cohort. Arthritis Rheum. 61, 1210-1217 (2009).
47. Bennell, K. L., Hunt, M. A., Wrigley, T. V., Lim, B. W. & Hinman, R. S. Role of muscle in the genesis and management of
knee osteoarthritis. Rheum. Dis. Clin. North Am. 34, 731-754 (2008).
48. Mikesky, A. E. et al. Effects of strength training on the incidence and progression of knee osteoarthritis. Arthritis Rheum. 55,
690-699 (2006) .
49. Thorstensson, C. A., Henriksson, M., von Porat, A., Sjödahl, C. & Roos, E. M. The effect of eight weeks of exercise on knee
adduction moment in early knee osteoarthritis—a pilot study. Osteoarthritis Cartilage 15, 1163-1170 (2007) .
50. Roos, E. M. & Dahlberg, L. Positive effects of moderate exercise on glycosaminoglycan content in knee cartilage: a
four-month, randomized, controlled trial in patients at risk of osteoarthritis. Arthritis Rheum. 52, 3507-3514 (2005).
51. Thorp, L. E. et al. The biomechanical effects of focused muscle training on medial knee loads in OA of the knee: a pilot,
proof of concept study. J. Musculoskelet. Neuronal Interact. 10, 166-173 (2010).
52. Ericsson, Y. B., Dahlberg, L. E. & Roos, E. M. Effects of functional exercise training on performance and muscle strength
after meniscectomy: a randomized trial. Scand. J. Med. Sci. Sports 19, 156-165 (2009).
53. Amin, S. et al. Quadriceps strength and the risk of cartilage loss and symptom progression in knee osteoarthritis. Arthritis
Rheum. 60, 189-198 (2009).
54. Brandt, K. D. et al. Quadriceps strength in women with radiographically progressive osteoarthritis of the knee and those with
stable radiographic changes. J. Rheumatol. 26, 2431-2437 (1999).
55. Sharma, L., Dunlop, D. D., Cahue, S., Song, J. & Hayes, K. W. Quadriceps strength and osteoarthritis progression in
malaligned and lax knees. Ann. Intern. Med. 138, 613-619 (2003).
56. Lim, B. W., Hinman, R. S., Wrigley, T. V., Sharma, L. & Bennell, K. L. Does knee malalignment mediate the effects of
quadriceps strengthening on knee adduction moment, pain, and function in medial knee osteoarthritis? A randomized

10 จาก 12 20/1/2554 8:36

Knee Osteoarthritis: Muscle Weakness, Sensory Dysfunction and ... http://www.medscape.org/viewarticle/733228_print

controlled trial. Arthritis Rheum. 59, 943-951 (2008).

57. Zhao, D. et al. Correlation between the knee adduction torque and medial contact force for a variety of gait patterns. J.
Orthop. Res. 25, 789-797 (2007).
58. Miyazaki, T. et al. Dynamic load at baseline can predict radiographic disease progression in medial compartment knee
osteoarthritis. Ann. Rheum. Dis. 61, 617-622 (2002).
59. Ettinger, W. H. Jr et al. A randomized trial comparing aerobic exercise and resistance exercise with a health education
program in older adults with knee osteoarthritis. The Fitness Arthritis and Seniors Trial (FAST). JAMA 277, 25-31 (1997).
60. Messier, S. P. et al. Exercise and dietary weight loss in overweight and obese older adults with knee osteoarthritis: the
Arthritis, Diet, and Activity Promotion Trial. Arthritis Rheum. 50, 1501-1510 (2004).
61. Chang, A. et al. Hip abduction moment and protection against medial tibiofemoral osteoarthritis progression. Arthritis
Rheum. 52, 3515-3519 (2005).
62. Hinman, R. S. et al. Hip muscle weakness in individuals with medial knee osteoarthritis. Arthritis Care Res. (Hoboken) 62,
1190-1193 (2010).
63. Bennell, K. et al. Hip strengthening reduces symptoms but not knee load in people with medial knee osteoarthritis and varus
malalignment: a randomised controlled trial. Osteoarthritis Cartilage 18, 621-628 (2010).
64. Sled, E. A., Khoja, L., Deluzio, K. J., Olney, S. J. & Culham, E. G. Effect of a home program of hip abductor exercises on
knee joint loading, strength, function, and pain in people with knee osteoarthritis: a clinical trial. Phys. Ther. 90, 895-904
(2010).
65. Block, J. A. & Shakoor, N. The biomechanics of osteoarthritis: implications for therapy. Curr. Rheumatol. Rep. 11, 15-22
(2009).
66. Konttinen, Y. T., Tiainen, V. M., Gomez-Barrena, E., Hukkanen, M. & Salo, J. Innervation of the joint and role of
neuropeptides. Ann. N. Y. Acad. Sci. 1069, 149-154 (2006).
67. Refshaug, K. M. Proprioception and joint pathology. Adv. Exp. Med. Biol. 508, 95-101 (2002).
68. Sharma, L. Proprioceptive impairment in knee osteoarthritis. Rheum. Dis. Clin. North Am. 25, 299-314 (1999).
69. Hurley, M. V., Rees, J. & Newham, D. J. Quadriceps function, proprioceptive acuity and functional performance in healthy
young, middle-aged and elderly subjects. Age Ageing 27, 55-62 (1998).
70. Pai, Y. C., Rymer, W. Z., Chang, R. W. & Sharma, L. Effect of age and osteoarthritis on knee proprioception. Arthritis
Rheum. 40, 2260-2265 (1997).
71. Koralewicz, L. M. & Engh, G. A. Comparison of proprioception in arthritic and age-matched normal knees. J. Bone Joint
Surg. Am. 82, 1582-1588 (2000).
72. Brandt, K. D. Neuromuscular aspects of osteoarthritis: a perspective. Novartis Found. Symp. 260, 49-58 (2004).
73. O'Connor, B. L., Visco, D. M., Brandt, K. D., Myers, S. L. & Kalasinski, L. A. Neurogenic acceleration of osteoarthrosis. The
effects of previous neurectomy of the articular nerves on the development of osteoarthrosis after transection of the anterior
cruciate ligament in dogs. J. Bone Joint Surg. Am. 74, 367-376 (1992).
74. Bennell, K. L. et al. Relationship of knee joint proprioception to pain and disability in individuals with knee osteoarthritis. J.
Orthop. Res. 21, 792-797 (2003).
75. Hall, M. C., Mockett, S. P & Doherty, M. Relative impact of radiographic osteoarthritis and pain on quadriceps strength,
proprioception, static postural sway and lower limb function. Ann. Rheum. Dis. 65, 865-870 (2006).
76. Felson, D. T. et al. The effects of impaired joint position sense on the development and progression of pain and structural
damage in knee osteoarthritis. Arthritis Rheum. 61, 1070-1076 (2009).
77. Shakoor, N., Furmanov, S., Nelson, D. E., Li, Y. & Block, J. A. Pain and its relationship with muscle strength and
proprioception in knee OA: results of an 8-week home exercise pilot study. J. Musculoskelet. Neuronal Interact. 8, 35-42
(2008).
78. Shakoor, N., Lee, K. J., Fogg, L. F. & Block, J. A. Generalized vibratory deficits in osteoarthritis of the hip. Arthritis Rheum.
59, 1237-1240 (2008).
79. Ageberg, E., Flenhagen, J. & Ljung, J. Test-retest reliability of knee kinesthesia in healthy adults. BMC Musculoskelet.
Disord. 8, 57 (2007).
80. Waxman, S. G. Clinical Neuroanatomy. Chapter 14: Somatosensory Systems [online], http://www.accessmedicine.com
/content. aspx?aID=5274328 (2010).
81. Shakoor, N., Agrawal, A. & Block, J. A. Reduced lower extremity vibratory perception in osteoarthritis of the knee. Arthritis
Rheum. 59, 117-121 (2008).
82. Lund, H. et al. Movement detection impaired in patients with knee osteoarthritis compared to healthy controls: a cross-
sectional case-control study. J. Musculoskelet. Neuronal Interact. 8, 391-400 (2008).

11 จาก 12 20/1/2554 8:36

Knee Osteoarthritis: Muscle Weakness, Sensory Dysfunction and ... http://www.medscape.org/viewarticle/733228_print

Acknowledgments
L. Barclay, freelance writer and reviewer, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the
MedscapeCME-accredited continuing medical education activity associated with this article.

Reprint Address
Unit for Musculoskeletal Function and Physiotherapy, Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Campusvej 55,
DK-5230 Odense, Denmark Ewa M. Roos, PhD eroos@health.sdu.dk

Competing interests
The authors, the journal Chief Editor J. Buckland and the CME questions author L. Barclay declare no competing interests.

Nat Rev Rheumatol. 2010;6(12) © 2010 Nature Publishing Group

This article is a CME certified activity. To earn credit for this activity visit:
http://www.medscape.org/viewarticle/733228

12 จาก 12 20/1/2554 8:36