Abstract:
Background: Osteoarthritis is the commonest
disorder of the synovial joints. It is potentially a very
disabling chronic disease often associated with pain and joint
stiffness among other symptoms. Pain is the main reason for the
patient seeking medical attention, therefore most forms of
therapy are aimed at achieving adequate pain relief. The use of
oral medications can be problematic with issues such as poor
patient compliance and various adverse drug reactions have been
credited to these drugs including the coxib group. In the
orthopaedic community in West Africa, there is now a move
towards the use of intra-articular injections (particularly
hyaluronic acid as sodium hyaluronate) as the primary treatment
option in knee osteoarthritis.
Aim:
To evaluate the short-term pain relief in patients with knee
osteoarthritis following the injection of 1% hyaluronic acid.
Study
Design and location: Prospective
study carried out at the University College Hospital, Ibadan,
South-Western Nigeria, West Africa.
Method: 20 consecutive patients with
clinical and radiological diagnosis of knee osteoarthritis seen
at the Orthopaedic outpatients clinic at the University College
Hospital, Ibadan, were entered into the study and were scheduled
to receive a total of three injections into the affected knee on
a weekly basis. The pain intensity was evaluated using the
Visual Analogue Scale (VAS) prior to each injection. 11 knees in
8 patients completed this study with the prescribed number of
intra-articular injections. An intention to treat analysis was
used.
Results: There was significant reduction in knee pain following each
injection (particularly between week 1 and week 3 injections)
and this was sustained over a short period of 12 weeks
follow-up.
Conclusion: In patients with knee OA who are also poor responders or
intolerant to non-steroidal anti-inflammatory drugs,
intra-articular Synject (1% hyaluronic acid) offers an
alternative but effective therapy for the relief of pain.
J.Orthopaedics 2008;5(1)e8
Keywords:
Osteoarthritis, Synovial joint, Hyaluronic
acid, Pain Relief
Introduction:
Osteoarthritis
(OA) is the commonest disorder of the synovial joints and the
primary form of the disease is strongly associated with aging1.
Although OA can affect smaller synovial joints, large joint
osteoarthritis (LJOA) is by far the most prevalent disease. Among the large joints, the knee is the most commonly
affected joint. With
the increase in the elderly population, LJOA is becoming an
increasingly health problem in Nigeria and indeed the West
African sub region. Most patients with knee OA seek medical
attention on account of joint pain, which is disabling, poorly
localized and usually aggravated by increase in daily activity.
The treatment modalities for OA are therefore directed at pain
relief before consideration is given to function or disability.
In
most instances, the first line drugs regularly prescribed for
the treatment of the pain associated with osteoarthritis
includes analgesics alone or in combination with non-steroidal
anti-inflammatory drugs. However, the chronicity of
osteoarthritis as a disease has resulted in non-compliance with
the use of oral medications in addition to the fact that considerable side effects accompany the
long-term use of these medicaments.
In
the past two decades, efforts to combat the poor compliance with
oral analgesics and non-steroidal anti-inflammatory drugs have
lead to the search for alternative modes of therapy. Various
studies have demonstrated the efficacy and convenience of
intra-articular injection of hyaluronic acid (as sodium
hyaluronate) in the treatment of pain in osteoarthritis of the
knee joint 2,3,4.
Hyaluronic
acid (HA) as hyaluronate is a high molecular weight
polysaccharide found in the synovial fluid as the sodium salt. It is found in many extracellular tissues including
synovial fluid, aqueous humor, skin extracellular tissues and it
is one of the main components of the extracellular matrix of the
articular cartilage where it forms the backbone to which
cartilage proteoglycan is attached via a link protein 3,5,6.
In
the synovial joints where it is produced by chondrocytes and
synoviocytes, HA acts as a viscosupplement in that it helps in
lubricating the joint, acts as a shock absorber and ensures
adequate articular cartilage nutrition3. These mechanical actions of HA therefore limit attrition
wear of the articular cartilage in the synovial joints. However,
in osteoarthritis, synovial fluid HA becomes depolymerised
resulting in a decrease in the molecular weight and subsequently
the viscoelasticity of this sugar7. The aftermath of
this change is an increase in the susceptibility of the
articular cartilage to attrition wears and cartilage flaking
leading to articular cartilage defect, which is the hallmark of
osteoarthritis. Ultimately, these changes contribute to the pain
experienced by patients with osteoarthritis of these joints.
Although
there have been reports from various parts of the world on the
effectiveness of hyaluronic acid in reducing pain in knee
osteoarthritis2,3,4 there has been no report in the
English literature of this treatment modality in Nigerian
patients. The aim of this study was to evaluate the efficacy of
1.0% hyaluronic acid in achieving pain relief in patients with
knee OA.
Material and Methods :
20
consecutive patients attending the Orthopaedic outpatient clinic
of the University College Hospital, Ibadan with clinical and
radiological evidence of osteoarthritis of the knee were
recruited into this study. Informed
consent was obtained and the pain
intensity
at presentation was evaluated using a Visual Analogue Scale.
(VAS). Knee
injections were carried out at weekly intervals and the VAS
scores were documented before each injection. Each treatment
intervention comprised a course of knee injections for each
affected joint.
Intraarticular
Injection Procedure
Under
aseptic conditions, a prepacked syringe of 1.0% hyaluronic acid
formulated as Synject (provided by FIDSON HEALTHCARE NIGERIA)
was injected into the lateral suprapatellar recess of the knees.
Each prepacked syringe vial contains; 20.0mg of sodium
hyaluronate Ph. Eur., 17.0mg of sodium chloride, 0.56mg of
disodium hydrogen phosphate dihydrate, 0.08mg of sodium
dihydrogen phosphate monohydrate and water for injection to make
it up to 2mls. In 4
knees, significant effusion was encountered and consecutively
drained prior to the Synject injection.
Results :
11 knees in 8 patients had 3 injections on a
once weekly basis as intended. However in the remaining 12 patients, seven felt that the
knee pains had reduced so significantly after the 2nd
injection that they declined further injections. The pre-treatment consent gave the participants the right
to discontinue treatment as evidenced by these satisfied
patients hence the withdrawal. In addition, five patients were
lost to follow-up after the first injection. The average
duration of knee pain prior to seeking western medical attention
was 11.4 years (range 3 years – 30 years) in the eleven knees
that were fully evaluated. Of the 8 patients that completed the
study, 6 were females and bilateral knee involvement occurred in
3 patients (2 females and 1 male patient).
Statistical
Methods
The
paired-t test statistic was used to investigate the hypothesis
of a zero change in pain following the use of hyaluronic acid to
relieve pain in osteoarthritis of the knee. Although there was
no control group that did not receive the injection or to which
a placebo or any other form of treatment was given, yet each
subject served as his/her own control.
In
these 11 knees, the mean visual analogue scale score during the
first visit and prior to the first injection was 5.91(SD±2.47),
this decreased to 3.42(SD±1.13) prior to the second injection
and further still to 2.82(SD±0.75) prior to the third injection
(Table 1).
The
reduction in pain was statistically significant between week 1
and week 2 injections (P<0.013) and very significant between
week 1 and week 3 injections (P<0.000). However, there was no
significant pain relief between week 2 and 3 injections
(P<0.132) (Table 2).
Affected Knees
Visual Analogue Scale Scores
|
Week
1
|
Week
2
|
Week
3
|
1
|
7
|
2
|
2
|
2
|
6
|
5
|
3
|
3
|
5
|
4
|
3
|
4
|
5
|
3
|
2
|
5
|
5
|
3
|
3
|
6
|
4
|
3
|
3
|
7
|
10
|
3
|
4
|
8
|
10
|
3
|
4
|
9
|
4
|
5
|
2
|
10
|
7
|
5
|
3
|
11
|
2
|
2
|
2
|
Mean
|
5.91
|
3.42
|
2.82
|
S.D
|
2.47
|
1.13
|
0.75
|
Table 1. Visual Analogue Scale (VAS)
scores prior to the weekly injections
|
Lower
|
Upper
|
t
|
P-values
|
Between week 1
& 2
|
0.64
|
4.27
|
3.019
|
0.013
|
Between week 1
& 3
|
1.77
|
4.27
|
5.197
|
0.000
|
Between week 2
& 3
|
-0.23
|
1.50
|
1.641
|
0.132
|
Table 2. Confidence Interval
Discussion :
Pain
and joint stiffness are the two principal symptorns associated
with OA1 but of these two, joint pain is the principal symptom
that necessitates the patients seeking medical attention.
Therefore in the management of osteoarthritis, more attention is
paid to pain relief sometimes at the expense of knee joint
deformities patient education, supervised exercises, reduction
in adverse mechanical factors and amenable risk factors like
obesity.
The
various pharmacological interventions that have been in use in
the treatment of pain due to osteoarthritis include
acetaminophen, non-steroid anti-inflammatory drugs (NSAIDs),
intra-articular injection of steroid or hyaluronic acid and
opioid analgesics for severe pain. However, in view of the
nature of the pain in OA, monotherapy is often not sufficient
and in most instances combinations of analgesics and NSAIDS are
commonly used1,8. These medicaments are not without adverse side
effects and because they have to be taken for long periods in
view of the chronicity of osteoarthritis, compliance is low and
many patients opt for alternative therapy including various
forms of intra-articular injections.
In
Southwestern Nigeria as in most parts of the country, patients
have a preference for parenteral modalities of treatment of most
ailments, as they believe that this mode of treatment is more
effective than oral medications. The drawback however is that most of these patients often
do not complete the regime of treatment as they discontinue
treatment a soon as they experience satisfactory improvement in
their symptoms (particular pain) and this was demonstrated in
this study.
Various
studies have shown that the intra-articular injection of hyaluronic acid (HA) as sodium
hyaluronate (Na-HA)
results in significant relief of joint pain due to
osteoarthritis2,3,4. This was also observed in this
study as the knee pain which was measured by the VAS scale
revealed statistically significant reduction following the 2nd
and 3rd weekly injections of HA compared with the
initial pain score on week 1. Altman and Moskowitz group found
that this effect was more pronounced in patients with poor
response to NSAIDs and also in those who are intolerant to
NSAIDs3. In our study group, all our patients,
usually as a result of the persistence of pain had used various
medications including NSAIDs, often as self-medications, prior
to seeking medical attention. The main limitation of this study
was the short follow-up period of 12 weeks. However, a similar
study by Altman and Moskowitz group revealed a sustained relief
of knee pain (after 26 weeks) following HA administration3.
This sustained pain relief is attributed to the fact that
exogenous HA (e.g Synject) has been shown to stimulate
endogenous HA production by the synoviocytes from osteoarthritic
joints9. The implication of this is that
administration of exogenous HA (e.g. Synject) acting, as a
viscosupplement will result in an immediate reduction in
articular cartilage friction and therefore pain. However, the
subsequent increased production of endogenous HA will sustain
the activity of this sugar thereby prolonging pain relief.
Conclusion:
Hyaluronic
acid injections provide an alternative treatment modality for
patients unresponsive or intolerant to NSAIDs. In the elderly
population in Nigeria, the incidence of peptic ulcer disease is
unknown but anecdotal evidence suggests that it will be
substantial due to the indiscriminate use of NSAIDs in the
country for a variety of illnesses. The use of hyaluronic acid
in treating knee osteoarthritis will be of particular value in
Nigerian elderly patients who may have concomitant knee OA and
are at a higher risk of developing peptic ulcer disease.
Acknowledgement:
The
authors wishes to thank Prof E A Bamgboye of the Department of
Epidemiology, Medical Statistics and Environmental Health
(EMSEH), College of Medicine, University of Ibadan, Ibadan for
his advice and also for the statistical analysis of the data.
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