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CASE REPORT

Intra-Articular Hyaluronic Acid (Synject) In The Management Of Osteoarthritis Of The Knee In Nigeria - An Initial Report

Alonge TO*, Ogunlade SO ,  Omololu  AB,  Ifesanya A,  Nottidge TE.

*Department of Orthopaedics and Trauma, University College Hospital, Ibadan.

Address for Correspondence:  

TO Alonge MD, FRCS
Department of Orthopaedics and Trauma   University College Hospital
Ibadan.
E
-mail:   alonget2003@yahoo.com

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.

Reference :

  1. Doherty M.  Pain in osteoarthritis In Pain 2002 – An updated review Refresher    Course Syllabus Giamberardino M. A. Ed. IASP Press Seattle, USA 2002. Pp 511.

  2. Bragantini A, Cassini M, De Bashani, G, Perbellini A. Controlled single blind trial     of intra-articularly injected hyaluronic acid (Hyalagan) in osteoarthritis of the knee     Clin. Trials J. 1987; 24: 333-340.

  3. Altman R, Moskowitz R, The Hyalgan Study Group. Ntraarticular sodium     hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: A     randomised clinical trial. J Rheum. 1998; 215(11): 2203-2212.

  4. Miltner O, Schneider U, Siebert CH, Niedhart C, Niethard F.U. Efficacy of    intraarticular hyaluronic acid in patients with osteoarthritis – A prospective clinical    trial. Osteoarthritis and Cartilage 2002; 10: 680-686.

  5. Hascall VC, Heinegard D. Aggregation of cartilage proteoglycans. 1.  The role of    hyaluronic acid. J. Biol Chem. 1974: 249: 4232 – 4241.

  6. Buckwalter J.A., Martin J. Degenerative Joint Disease. Ciba Clinical Symposium    1995: 47 (2): 6-7.

  7. Balazs EA. The physical properties of synovial fluid and the special le of     hyaluronic acid. In: Helfet J. Disorders of the knee. 2nd edition. Philadelphia:     Lippincott; 1974: 63-75.

  8. Bijlsma JW. Analgesia and the patient with osteoarthritis.    Am. J Ther. 2002; 9:189-197.

  9. Smith MM, Ghosh P. The synthesis of hyaluronic acid by human synovial    fibroblasts is influenced by the nature of the hyaluronate in the extracellular    environment. Rheumatol Int, 1987; 7 : 113-122.

This is a peer reviewed paper 

Please cite as : Alonge TO : Intra-Articular Hyaluronic Acid (Synject) In The Management Of Osteoarthritis Of The Knee In Nigeria - An Initial Report

J.Orthopaedics 2008;5(1)e8

URL: http://www.jortho.org/2008/5/1/e8

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