the importance of the intact limb for preservation of mobil-
ity and functional independence in individuals with unilat-
eral lower limb amputation, risk factor identi
fication, and
early disease detection appear to be of high importance for
effective prevention and rehabilitation of knee OA in this
patient population.
KNEE OA PATHOMECHANICS AND RISK FACTORS
The knee is one of the joints most commonly affected by OA
with a 50% lifetime risk of developing symptomatic disease
in the general population.
5
As there is no cure, conservative
management of knee OA has traditionally focused on pain
management and improving overall mobility. However, due
to the degenerative nature of the disease, knee OA commonly
progresses to a stage where joint replacement surgery may
be the only viable option for alleviating symptoms and
improving function and QOL. However, joint replacement
surgery may not be a feasible option for some patients such
as those with lower limb amputation or other concomitant
comorbidities. Therefore, attempts are currently underway to
identify potentially modi
fiable risk factors and implement
joint protective strategies that can result in favorable long-
term outcomes.
Although knee OA has long been viewed as a non-
in
flammatory “wear and tear” of the articular cartilage in
older adults, this disease paradigm is rapidly changing. There
is now mounting evidence that although OA is a mechani-
cally driven condition, the disease process is chemically
mediated through a complex interplay between systemic and
nonsystemic factors.
6,7
Normal articular cartilage has a unique
load-bearing mechanism capable of tolerating customary daily
loads without sustaining injury that is determined through
contributions from genetics,
8
as well as mechanical
9
and age-
related factors.
10
However, long-term exposure to excessive
loads and other changes in joint mechanics, similar to those
observed after lower limb amputation,
11
–14
can lead to adap-
tive cellular responses and altered gene expressions that facili-
tate the onset and progression of the disease.
7,15
Although systemic risk factors such as genetic predisposi-
tion
16
may increase the risk of knee OA development after
traumatic limb amputation through gene-speci
fic and time-
dependent alterations in gene expression, e.g., these factors
are permanent and nonmodi
fiable, which makes them unlikely
as direct preventative or therapeutic targets. Conversely, pre-
viously identi
fied nonsystemic and potentially modifiable risk
factors such as chronic knee pain,
17,18
obesity,
19,20
abnormal
knee joint mechanics,
6,7
lower limb muscle weakness,
6,21
pre-
vious joint trauma,
22
and altered physical activity levels
23,24
are all modi
fiable through preventative and rehabilitative strat-
egies that could be applied to individuals with lower limb
amputation. Therefore, the purpose of this narrative review is
to organize the pertinent literature in an effort to identify
nonsystemic, potentially modi
fiable risk factors related to the
development and progression of knee OA in the sound limbs
of Service Members with traumatic amputations and identify
possible prevention and treatment solutions.
REVIEW CRITERIA
Electronic searches of PubMed and EMBASE databases were
performed in July 2015. MeSH terms for the initial search
included
“knee,” “OA,” “amputation,” and “trauma.” A com-
prehensive search was performed for each nonsystemic,
OA-related risk factor by combining the initial search strat-
egy with the combination of the following keyword search
terms:
“pain,” “obesity or body mass index or BMI,” “bio-
mechanics or load or force or moment or rate,
” “muscle and
(weakness or strength or symmetry),
” “acute joint injury or
trauma,
” and “physical activity or sports participation.” All
titles and abstracts were screened for content and pertinence
to the purpose of the review. In cases where direct evidence
was lacking, additional supplemental manual searches were
performed for relevant articles based on reference lists of the
retrieved articles or relevant published literature related to
knee OA and its risk factors in the general population.
CHRONIC KNEE PAIN
Presence of chronic knee pain has been deemed as an early
indicator of degenerative joint changes that may appear
before evidence of radiographic knee OA in nonamputees.
17
The commonly used conventional radiographs are known to
be insensitive to detecting early OA structural changes and
are often only useful in measuring late-stage disease.
25
More
recently it has been suggested that symptoms often precede
the appearance of radiographic abnormalities, implying the
existence of a potentially detectable
“prodromal phase” in
the transition from preradiographic to radiographic stages
of OA.
18
As such, knee pain with activities associated with
higher dynamic knee loading such as climbing stairs has been
suggested to help identify individuals with preclinical knee
OA suitable for early intervention strategies.
17,18
Furthermore,
presence of chronic knee pain has been identi
fied as an early
sign of future OA-related risk of functional decline.
26
After lower limb amputation, high knee pain prevalence
rates of 50 to 55% and 36 to 38% have been reported in
the intact limbs of individuals with unilateral transfemoral
and transtibial amputations, respectively, compared to only a
20% prevalence rate among nonamputees.
3,27,28
Conversely,
the residual knee on the side of a transtibial amputation
has been reported to be
five times less likely to be painful
compared to matched knees in nonamputees.
3
Furthermore,
Burke et al
29
reported a knee pain prevalence rate of 52% in
the intact limbs of individuals with unilateral transtibial
amputations as compared to no reports of pain in the resid-
ual side knee. The higher prevalence of knee pain on the
side of the intact lower limb in individuals with unilateral
amputation is consistent with the patterns of knee OA
reported in this patient population and may be a sign of
MILITARY MEDICINE, Vol. 181, November/December Supplement 2016
39
Development of Knee Osteoarthritis After Unilateral Lower Limb Amputation