Medical Hypotheses 76 (2011) 887–892

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Medical Hypotheses
journal homepage: www.elsevier.com/locate/mehy

Clinical and economic consequences of the treatment gap in knee osteoarthritis

management
Nicholas J. London a, Larry E. Miller b,c, Jon E. Block c,⇑
a
Department of Orthopaedic Surgery, Harrogate District Foundation Trust, Harrogate HG2 7SX, United Kingdom
b
Miller Scientific Consulting, LLC, 1538 West University Heights Drive South, Flagstaff, AZ 86001, United States
c
Jon E. Block, Ph.D., Inc., 2210 Jackson Street, Suite 401, San Francisco, CA 94115, United States

a r t i c l e i n f o a b s t r a c t

Article history: Osteoarthritis affects 27 million American adults of all ages and is a leading cause of disability in middle-
Received 9 November 2010 aged and older adults. Initial management of knee osteoarthritis symptoms utilizes conservative care
Accepted 27 February 2011 although long-term efficacy is poor. Arthroplasty and high tibial osteotomy may be considered for
patients with severe pain or disability. We hypothesize that a distinct treatment gap exists for the patient
with symptomatic knee osteoarthritis who is unresponsive to conservative care (including simple
surgical treatments) yet refuses to undergo or is not an appropriate candidate for more invasive surgical
procedures. This treatment gap represents a protracted period in which the patient experiences debilitat-
ing pain, reduced quality of life, and a significant financial burden. Approximately 3.6 million Americans
linger in the knee osteoarthritis treatment gap and this number will grow to about 5 million people by
2025. The typical knee osteoarthritis treatment gap extends 20 years although the younger osteoarthritis
patient is faced with the treatment gap throughout the majority of their adult life. There is great need for
a safe, effective, and cost effective treatment option for patients with moderate to severe osteoarthritis
that enjoys high patient acceptance.
Ó 2011 Elsevier Ltd. All rights reserved.

Background management of knee OA symptoms utilizes conservative care

Osteoarthritis (OA) is a degenerative joint disease with no
known cure that is characterized by joint pain and dysfunction
caused by progressive articular cartilage loss [1]. Osteoarthritis af-
fects 27 million American adults of all ages [2] with the prevalence
exponentially increasing at 50 years of age in men and at 40 years
in women [3,4]. This condition is a leading cause of disability in
middle-aged and older adults [5]. Aside from compromising phys-
ical function and quality of life, OA is also responsible for a sub-
stantial economic burden, accounting for $128 billion per year in
direct and indirect costs [6–8]. With the continued aging of the
population and rising obesity rates, the prevalence of OA is esti-
mated to increase 40% by 2025 [9,10]. Overall, the clinical and eco-
nomic burden of OA will continue to increase and will remain a
major medical problem for decades to come.
Hypothesis
Although a wide range of treatments are available to the patient
with knee OA, each option suffers from distinct limitations. Initial
⇑ Corresponding author. Tel.: +1 415 775 7947; fax: +1 415 928 0765.
E-mail addresses: larrymiller@jonblockphd.com (L.E. Miller), jonblock@jon
blockphd.com (J.E. Block).
including activity modification, weight loss, physical therapy,
orthotics, and/or bracing. Anti-inflammatory and/or analgesic
medications, intra-articular hyaluronic acid and/or steroid injec-
tions, and arthroscopic lavage and debridement are often utilized
when initial conservative measures fail although their long-term
efficacy is poor [11,12] and they may actually encourage greater
mechanical loading of the medial compartment [13], resulting in
accelerated OA progression [14,15]. As the disease slowly pro-
gresses to cause moderate-to-severe pain and/or disability, total
knee arthroplasty represents the mainstay treatment although uni-
compartmental arthroplasty or high tibial osteotomy (HTO) may
be considered in select patients with single compartment disease.
Based on this typical treatment algorithm, we hypothesize that
there is a definitive treatment gap for the patient with symptom-
atic knee OA who is unresponsive to conservative care yet refuses
to undergo or is not an appropriate candidate for invasive surgical
procedures.
This treatment gap, defined as the time from unsuccessful
exhaustion of conservative treatment to surgical intervention, is
not a benign period. In fact, it represents a protracted period of
years and often decades in which the patient experiences debilitat-
ing pain, reduced quality of life, and a significant financial burden.
The reasons for the treatment gap in knee OA management are
threefold—ineffectiveness of conservative measures in the long-
term management of OA symptoms, lack of safe and effective

0306-9877/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.mehy.2011.02.044
888 N.J. London et al. / Medical Hypotheses 76 (2011) 887–892
minimally invasive treatments for knee OA, and a great reluctance
or unwillingness of patients to undergo a major and irreversible
surgery like arthroplasty or HTO, particularly in the younger OA
patient.
Hypothesis evaluation
How many patients are in the treatment gap?
The number of patients that languish in the knee OA treatment
gap has not been characterized but may be estimated by extrapolat-
ing from relevant sources. The proportion of adults who suffer from
symptomatic knee OA is 6% in people 30 years and older [16] and
15.2% in people 45 years and older [17]. Based on the age distribu-
tion of the United States population [18], it can be determined that
approximately 18 million Americans are currently living with symp-
tomatic knee OA. Of these patients, 23% (4.1 million) have difficulty
with ambulation [19], which implies conservative treatment failure
and arguably indicates the need for arthroplasty or HTO. However,
only 500,000 knee arthroplasties and HTOs are performed each year
in the United States, representing 13% of all patients with debilitat-
ing symptoms [20]. The remaining 17.5 million Americans suffer
from knee OA pain and dysfunction and 3.6 million experience unre-
solved debilitating pain despite unsuccessful attempts at symptom
amelioration with conservative therapy (Fig. 1). This latter group
of patients lingers in the treatment gap, represented by failures of
conservative therapies but unwillingness to undergo invasive, irre-
versible knee surgery. The treatment gap will continue to expand
with more new patients entering this period after exhausting at-
tempts at conservative care but with fewer patients leaving the
gap because of low arthroplasty utilization and increasing life
Fig. 1. Estimated number of patients in the treatment gap. Of the 18 million
patients with symptomatic knee osteoarthritis in the United States, 3.6 million are
in the treatment gap because they have difficulty with ambulation despite
conservative care but do not undergo knee arthroplasty or high tibial osteotomy.
HTO, high tibial osteotomy; OA, osteoarthritis.
expectancies. Thus, the burden of the treatment gap will likely ex-
pand to affect up to 5 million Americans by 2025 [9,10].
What is the duration of the treatment gap?
The duration of the treatment gap is largely unknown. Conser-
vative treatments such as analgesic and anti-inflammatory medi-
cations, bracing, and orthotics are generally initiated at the onset
of OA pain. Intra-articular hyaluronic acid injections are usually
withheld until at least 3 months of unsuccessful analgesic use.
Since these injections offer only short-term relief and the safety
and effectiveness of multiple injections over a lifetime are un-
known, there is no other accepted treatment to halt or reverse knee
OA progression until the end-stage has been reached. The typical
patient experiences knee OA symptoms for 9–12 years before
choosing to undergo arthroplasty [21–23]. However, the typical
duration of the treatment gap is likely much longer than this since
few patients who are eligible for arthroplasty actually undergo the
procedure. With an average age of symptom onset of 58–61 years
[21–23] and a mean US life expectancy of 78 years [24], the aver-
age knee OA treatment gap likely approaches 20 years since the
majority of patients ultimately refuse arthroplasty (Fig. 2). The
treatment gap is of particular concern in the younger OA patient.
Given that 38% of OA patients are under the age of 55 years and
10% are under 35 years [25], the younger OA patient is faced with
the treatment gap throughout the majority of their adult life.
Who is in the treatment gap?
Thus far, we have identified that at least 3.6 million Americans
are in the treatment gap at any given time and that the treatment
gap likely endures for an average of 20 years in most knee OA pa-
tients, but potentially for 40 or more years in the young OA patient.
But what are the characteristics of the patients that comprise the
treatment gap? The prevalence of knee OA is strongly related to ad-
vanced age with symptom onset generally occurring around
60 years of age [21–23] although OA cases presenting in their 20s
and 30s are not uncommon. In fact, 3.0% of OA patients are younger
than 25 years, 7.5% are 25–34 years, 12.6% are 35–44 years, and
15.2% are 45–54 years [25]. Therefore, people of all ages may present
with this disease and treatment decisions should, in part, consider
the wide variation in expected patient life expectancy.
Additional characteristics of knee OA patients are obesity [26]
and chronic physical activity [27] or occupational loads [28], all
of which contribute to excessive knee joint loading. The typical
OA patient also suffers from comorbidities including dyslipidemia,
renal impairment, and diabetes [29] and over 4 in 10 OA patients
over 35 years of age regularly take antihypertensive medication
[30].
Patients who remain in the treatment gap have experienced no
or marginal success with conservative treatments. Distinct differ-
ences exist in these patients versus those who elect to undergo
arthroplasty. The primary predictor of arthroplasty is a willingness
to undergo the procedure. Aside from perception of the procedure,
patients in poor health and with less severe dysfunction reject
arthroplasty more often [31]. Anticipated postoperative outcomes
also impact the decision to undergo arthroplasty; common reasons
for denying arthroplasty include high perceived surgical risk, reluc-
tance to undergo a surgical procedure, a belief that arthroplasty is
ineffective, and unwillingness to accept the potential risk of future
revision surgery [32,33]. This last determinant is especially impor-
tant to the younger OA patient given that arthroplasty survival is
shorter in these patients [34] and, therefore, they would be sub-
jected to multiple future surgeries. However, for the patients
who reject arthroplasty, no treatment is available to satisfactorily
alleviate OA symptoms and, therefore, pain and disability endures
 N.J. London et al. / Medical Hypotheses 76 (2011) 887–892
Fig. 2. Estimated duration of the treatment gap. The typical duration of the treatment gap in patients who undergo arthroplasty is 10 years. However, the treatment gap
endures for the remainder of life (20 years based on average osteoarthritis onset age and average life expectancy) in the 75% of patients who refuse arthroplasty. The
younger osteoarthritis patient may remain in the treatment gap for up to 40 years without surgical intervention. IHA, intra-articular hyaluronic acid; OA, osteoarthritis; PT,
physical therapy.
throughout the remainder of life. In fact, recently published survey
data in over 4700 older adults found that arthritis was strongly
associated with pain at the end of life irrespective of terminal diag-
nosis [35]. This dilemma underscores the need for safe and effec-
tive minimally invasive treatment options that can be offered to
the OA patient earlier in the course of disease without regard for
age or comorbidities.
Clinical consequences of the treatment gap
A number of conservative measures are recommended to allevi-
ate symptoms of mild to moderate knee OA; however, there is little
evidence to support the efficacy of these interventions [36]. Treat-
ment efficacy of a therapy can be quantified by reporting an effect
size (ES), which is a standardized measure of the mean difference
between a treatment and control group. For reference, an ES of
0.2 is considered a small treatment effect, 0.5 is moderate, and
0.8 or greater is a large treatment effect [37]. The ES of various con-
servative therapies for knee OA pain are 0.1 for ultrasound, 0.2 for
acetaminophen and arthroscopic debridement/lavage, 0.3 for non-
steroidal anti-inflammatory drugs and knee strengthening exer-
cises, and 0.6 for short-term relief with intra-articular hyaluronic
acid injections [36]. Little data are available to form a conclusion
on the efficacy of knee braces and orthotics; however, it is well-
established that subject compliance with these treatments is low
over the long term [36]. Overall, these low effectiveness estimates
are not surprising since these therapies do not alter the course of
the disease but only serve as palliative measures [38].
Knee pain generally worsens over time in OA patients [39].
Therefore, patients who fail conservative care likely endure chronic
pain, lower quality of life, and physical activity limitations, despite
continued analgesic and anti-inflammatory medication use. Over
time, the risk of weight gain, depression, chronic disease, and other
conditions manifested by lack of physical activity may increase
[40]. Most patients with knee OA also have concomitant comorbid
conditions although their relationship to OA is controversial [41].
Once conservative care options have been exhausted, the pa-
tient is faced with a difficult decision—to endure continued pain
and disability for the remainder of life while avoiding surgery or
to choose surgery and accept the associated risks and expenses.
Only 9–33% of patients with severe knee OA are willing to consider
knee arthroplasty despite the established effectiveness of this pro-
cedure [31,33,42]. Unicompartmental arthroplasty and HTO are
somewhat less effective than total knee arthroplasty, are reserved
only for patients with single compartment disease, and have
889
similarly low patient acceptance, largely because of the invasive
irreversible nature of the procedures as well as the extended recov-
ery time and potential need for future revision. Therefore, the
treatment gap endures for the remainder of life in most knee OA
patients.
Economic consequences of the treatment gap
OA is responsible for $128 billion per year in direct and indirect
costs [6–8], which equates to an economic burden of $4741 per pa-
tient per year when accounting for the 27 million Americans af-
flicted with this disease. Given that 3.6 million people comprise
the knee OA treatment gap, the total annual costs associated with
this therapeutic void is 17 billion dollars each year. Furthermore,
the number of OA patients as well as the volume and costs of pri-
mary and revision arthroplasty, are expected to rise exponentially
over the next few decades [9,10,43]. Consequently, the total eco-
nomic burden of the treatment gap in knee OA may rise to 24 bil-
lion dollars by 2025, conservatively assuming similar annual
patient costs [9,10]. Clearly, the economic impact of the treatment
gap in knee OA represents a significant societal burden and there is
an obvious need for safe and effective interventions that can alle-
viate pain and disability and, consequently, help to delay or avoid
arthroplasty.
The cost effectiveness of medical interventions can be charac-
terized by cost per quality-adjusted life year (QALY), which consid-
ers the quantity and quality of life gained by an intervention in
relation to the cost [44,45]. The quantity and quality of life is com-
monly expressed using a measure known as a QALY. One QALY rep-
resents 1 year in perfect health, a score of 0 QALYs represents
either death or 1 year in a coma, and negative values are some-
times utilized to represent severe conditions such as confinement
to a bed or inability to perform daily activities [46,47]. For exam-
ple, if a particular therapy extends patient life by 2 years and the
quality of life during this period was rated at 0.7 on a 0 to 1 scale,
then the therapy is said to generate 1.4 (2 years  0.7) QALYs. In
order to calculate cost effectiveness, the cost of the procedure is di-
vided by the number of QALYs gained. For example, a $20,000 pro-
cedure that generates 4 additional QALYs ($5000 per QALY) is
much more cost effective than a $15,000 procedure that results
in 1.5 additional QALYs ($10,000 per QALY).
Although great disparity exists in the interpretation of the cost
effectiveness of a treatment, interventions that cost between
$7000 and $22,000 per QALY are generally deemed cost effective
and those costing over $37,000 per QALY are cost prohibitive
890 N.J. London et al. / Medical Hypotheses 76 (2011) 887–892

[48]. Yet, it has been estimated that patients with knee OA are only
willing to pay up to $5700 per QALY for a treatment [49]. There-
fore, knee OA treatments must be especially cost effective before
the typical patient would consider utilizing the therapy. Unfortu-
nately, no known treatment for knee OA with established efficacy
has a cost per QALY below this willingness to pay threshold.
The total costs of oxycodone (with or without acetaminophen)
treatment over 4 months are approximately $9000 and cost-
effectiveness is estimated at $76,000 per QALY [50]. The cost-
effectiveness of NSAIDs is somewhat better with COX-2 specific
NSAIDS yielding $33,000 per QALY and non-specific NSAIDS yielding
$15,000 per QALY [51]. Among other common conservative mea-
sures, cost effectiveness (per QALY) is $6000 for knee bracing,
$8000 for clinic-based exercise programs, $11,000 for a primary care
weight loss program, and over $1 million for home-based exercise
although poor patient compliance limits the long-term utility of
these measures. Arthroscopic lavage has extremely poor efficacy
for the knee OA patient, which is reflected in a cost-effectiveness
estimate of over $1 million per QALY [51].
Total knee arthroplasty is considered one of the most cost effec-
tive surgical procedures in medicine [52,53] at an average of
$11,000 to $18,000 per QALY [36,49]. Cost effectiveness of unicom-
partmental arthroplasty for single compartment disease is similar
to total knee arthroplasty [54–56]. From a practical perspective,
however, arthroplasty remains cost prohibitive for the OA patient
considering that the average willingness to pay per QALY is much
lower than the actual cost per QALY for this procedure. This discor-
dance may partially explain why only a small proportion of pa-
tients with need for arthroplasty are willing to undergo the
procedure [33,42]. Cost effectiveness data on HTO procedures are
unavailable.
When considering therapeutic effectiveness and cost utility, no
current OA treatment option offers the combination of excellent
therapeutic effectiveness and cost effectiveness (Fig. 3).
Summary
Overall, conservative treatments for knee OA are largely ineffec-
tive over the long-term and arthroplasty and HTO are considered
by only a minority of appropriate patients. Furthermore, none of
these interventions can be deemed as cost effective when consid-
ering patient willingness to pay only $5700 per QALY. Even in sub-
jects willing to undergo arthroplasty, only 1 in 4 subjects with
disabling knee OA ultimately opt for this procedure since most pa-
tients believe that OA pain and disability must be extreme before
arthroplasty should even be considered [31]. Practically, this sug-
gests that the patient with moderate or severe knee OA pain or dis-
ability who has failed conservative treatment may choose to delay
arthroplasty for years, decades, or even indefinitely. A study of 94
candidates for knee arthroplasty reported a mean pain duration of
11 years and mean disability duration of 7 years [57]. Given that
most arthroplasty candidates decline surgery, these are likely
conservative estimates and the duration of the treatment gap
may approach 20 years or longer in many patients. This protracted
treatment gap, a period during which the patient endures chronic
pain and disability and where substantial economic resources are
depleted, highlights the great need for a safe, effective, less

Fig. 3. Effectiveness and cost utility of common treatments for knee osteoarthritis. Numerous knee osteoarthritis treatments are considered cost-effective although only total
knee arthroplasty is considered to be clinically effective and cost effective. However, given that the typical knee osteoarthritis patient is only willing to pay up to $5700 per
quality-adjusted life year, no existing knee osteoarthritis treatment offers the ideal combination of clinical effectiveness and cost effectiveness below the willingness to pay
threshold. COX-2, cyclooxygenase-2; IHA, intra-articular hyaluronic acid; NSAIDS, nonsteroidal anti-inflammatory drugs; QALY, quality-adjusted life year; TKA, total knee
arthroplasty; UKA, unicompartmental knee arthroplasty.
 N.J. London et al. / Medical Hypotheses 76 (2011) 887–892
invasive, and more cost effective treatment option for patients
with moderate to severe OA that enjoys high patient acceptance.
In contrast to analgesic medications that alleviate pain only,
disease-modifying OA drugs such as bisphosphonates, calcitonin,
and cytokine inhibitors have been developed with the goal of slow-
ing or completely arresting OA progression [58]. However, none of
these agents has proven to provide long-term therapeutic benefit
[59].
Minimally invasive, implantable medical devices have enjoyed
growing utilization over the last decade in the fields of cardiology,
vascular medicine, and orthopedics among others. However, there
are currently no FDA-approved minimally invasive medical devices
intended to treat knee OA. Characteristics of an ideal treatment
method for patients with knee OA unresponsive to conservative
measures include a minimally invasive procedure that significantly
improves pain and disability and results in biomechanical and/or
unloading alterations that may slow [60,61] or potentially reverse
[62] OA progression. Since lower extremity OA onset and progres-
sion are largely mediated by excessive and/or abnormal loading
across the joint [63,64], technologies that absorb or transfer loads
away from the affected compartment(s) have great potential in the
treatment of this disabling condition. Such a technology may be ac-
cepted by more patients, which may allow an expanded number of
patients to undergo intervention earlier, thereby saving years of
debilitating pain, improving quality of life, and reducing medical
costs. Since arthroplasty is the main driver of the large treatment
cost of knee OA, delaying or avoiding arthroplasty altogether
may lower the total OA burden from a clinical and economic per-
spective. Furthermore, delaying the need for arthroplasty will re-
duce the need for future revision surgery, which is costlier and
associated with more complications versus first-time procedures
[65]. A review of clinicaltrials.gov (November 5, 2010) shows 648
clinical trials on the topic of knee OA but none that utilize mini-
mally invasive implantable medical devices.
In summary, conservative care options for knee OA treatment
yield less than satisfactory results with little impact on disease
progression. The treatment gap in knee OA management is an
underappreciated period of 20 years or more in many cases that re-
sults in enormous clinical and economic consequences for millions
of Americans. Despite the fact that arthroplasty was introduced
over 50 years ago for treatment of moderate-to-severe knee OA,
it remains the mainstay treatment. However, it represents an ab-
ject failure of conservative, nonoperative management of this con-
dition. Consequently, there is a great need for minimally invasive,
reversible treatments with high patient acceptance and excellent
safety and efficacy to fill the large OA treatment gap. To date, no
such treatment exists for the patient suffering from knee OA.
Conflict of interest statement
Moximed, Inc. (Hayward, CA) provided financial support for
development of this manuscript.
Acknowledgements
We thank Mr. Randy Asher for assistance with graphical illus-
trations. Moximed, Inc. (Hayward, CA) provided financial support
for development of this manuscript. The authors controlled the
decision to submit this manuscript for publication.
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