The Use of Non-Steroidal Anti-inflammatory Drugs in Phonophoresis Treatment for Knee

Osteoarthritis: A Literature Review

Submitted by: Brenda Casanova, Alex Grodzicki, Erin Reetz, and Carly Siko
 I. INTRODUCTION

Osteoarthritis is one of the most common rheumatological diseases. The disease is

characterized by the breakdown of articular cartilage causing pain, stiffness and decreased range

of motion in synovial joints.1 The knee is one of the most commonly affected joints often causing

disability. The intentions of osteoarthritis treatment are to relieve pain, increase joint mobility,

and increase day to day function and activities of daily living (ADLs).2 A variety of non-

pharmacological and pharmacological treatments have been recommended for treating

osteoarthritis. Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) is widely

used, however, oral NSAIDs are typically associated with having gastrointestinal side effects.1 

A method that can be used for treatment of osteoarthritis is phonophoresis, an application

of ultrasound that increases the absorption of topical agents through dermal layers in the skin.3

Topical agents commonly used with phonophoresis include steroids, salicylates, anesthetic

agents, methyl nicotinate, and NSAIDs.1 These topical agents can be in gel or cream form and

are applied using either pulsed or continuous ultrasound techniques.3 According to the

Michlovitz et al3 text, there have been inconclusive results for the treatment of pain using various

topical agents delivered by either pulsed or continuous ultrasound. Based on the literature

findings, the focus of this literature review will be the effects of phonophoresis on knee

osteoarthritis through a variety of parameters including types of NSAIDs as topical agents, the

treatment parameters of the ultrasound machine (power output, frequency, treatment duration),

and method of ultrasound (pulsed or continuous).

II. DISCUSSION

From the review of available literature, there are several different NSAIDs that are

typically used in phonophoresis treatment for knee osteoarthritis. The topical agents used include
diclofenac, piroxicam, methyl salicylate, and ibuprofen, which can be in cream or gel form. Of

the studies reviewed, two studies used diclofenac1, 2, two used piroxicam4, 6, one used methyl

salicylate2, and one used ibuprofen6. Four out of the five studies1,2,4,6 used a gel-based topical

agent. There were two studies using gel-based and cream-based topical agents.2,6 The study using

ibuprofen as the topical agent compared the use of ibuprofen in gel and cream form for

phonophoresis treatments6. The gel and cream in this study contained 5% ibuprofen6. The

purpose in using a gel versus a cream during phonophoresis treatments involves the properties of

the drug enhancing or inhibiting transcutaneous transmission via ultrasonic energy6. The

outcome measures for pain and knee function were recorded using the Visual Analog Scale

(VAS) and Western Ontario and McMaster Universities (WOMAC) score respectively6, which

were common outcome measures across all five studies reviewed. The within-group results of

the study concluded that the VAS pain measures improved from pre-treatment to post-treatment

for both ibuprofen gel- and cream-based topical agents6, and that the total WOMAC score also

showed statistical significance from pre- to post-treatment measurements.6 However, when

comparing between the two treatment groups, the group that received the gel-based topical agent

had greater statistical significance in pre- and post-treatment measurements for both VAS pain

measures and total WOMAC score.6 According to the study, the gel may have had better affect in

reducing pain and increasing functionality of subject knees due to “increased acoustic

transmission capability, from decreased attenuation and reflection.”6

Another study by Akinbo et al examined the efficacy of two different NSAIDs,

diclofenac sodium, a gel-based agent, and methyl salicylate, a cream-based agent 2. The findings

of this study showed that diclofenac phonophoresis, methyl salicylate phonophoresis and

conventional ultrasound were effective in relieving symptoms in patients with knee

osteoarthritis2. However, diclofenac phonophoresis was found to be slightly more effective

compared with the other two methods (p<0.05)2. Additionally, methyl salicylate phonophoresis

did not show statistical significance when compared to the ultrasound treatment in relieving

symptoms of pain in patients with knee osteoarthritis2, which further indicates that cream topical

agents are not as effective in pain reduction in phonophoresis application on subjects with knee

osteoarthritis.

It is understandable that a gel-based topical agent would be the better option for

phonophoresis treatment due the nature of the substance. Ultrasonic energy is better attenuated

through substances that have a greater density due to the ability to offer greater resistance in

molecular motion, also known as acoustic impedance.3 The Michlovitz et al text confirms the

results of the study in that cream- or ointment-based topical agents have a low transmissivity,

meaning that less of the medication gets through the skin during treatment, rendering the cream-

or ointment-based agent less effective in treatment than its gel-based counterpart.3

Another parameter that can be manipulated during phonophoresis treatments are the

properties of the ultrasound machine. The purpose of the phonophoresis treatment is to “push”

the topical agent through the skin with the permeability of the skin being increased by the

physical properties of the ultrasound treatment, therefore variations in dosage will have an effect

on the efficacy of the treatment. Variances and commonalties were found among the studies

reviewed that included number of treatments and dosage, which includes treatment session

duration, frequency, and power output. All studies reviewed had a similar number of treatment

sessions. The standard number of treatment sessions was 10 sessions total with the majority of

studies selecting 5 sessions per week for two weeks2,4,5,6, and one study performing 10 sessions

over 10 consecutive days1. As the treatments of phonophoresis and ultrasound are typically
short-term treatments for osteoarthritis3, the common duration selected for treatments in the

studies is understandable.

The dosages among the studies were also quite similar. All five studies used a frequency

of 1 MHz for continuous ultrasound application1,2,4,5,6. Four2,4,5,6 of the five studies used a power

output/intensity of 1.0 W/cm2. One study1 used a power output/intensity of 1.5 W/cm2.

Additionally, the duration of each treatment session lasted for five1,2,5 to ten4,6 minutes. It is

recommended in the Michlovitz et al3 textbook that for the treatment of arthritis using ultrasound

techniques that the parameters for treatment are set to “three times per week for 5 to 10 minutes

per treatment using 1MHz, continuous ultrasound set at 1 to 2 W/cm2 for 2 to 3 weeks.” With

increasing frequencies, there is a greater risk of additional thermal effects of the ultrasound

application, which is not the intention of the phonophoresis treatment.3 However, it is also

suggested that these thermal effects may also increase the permeability of the skin, allowing

more of the topical agent to be transmitted to the treatment tissue3. This leads to the

inconclusiveness of dosage in phonophoresis treatment versus traditional ultrasound for knee

osteoarthritis.

Another parameter that is varied in phonophoresis treatments is the delivery method of

pulsed or continuous ultrasound. Of the articles reviewed, all five contained the parameter of

using continuous ultrasound for topical agent delivery during phonophoresis treatment. While

there are is a limited amount of studies that have been performed comparing continuous and

pulsed ultrasound, one of the studies reviewed did compare the delivery of diclofenac through

pulsed and continuous ultrasound.1 In the study, one group received diclofenac treatments with

continuous ultrasound and the other group received diclofenac treatments with pulsed ultrasound

at a 20% duty cycle with intensity (power output) remaining the same for both groups.1 While
the results of this study showed statistically significant improvements in VAS pain at rest and in

activity, WOMAC scores and physical function scores for all groups after treatment (p<0.05)1

showed no significant difference among any of the outcome measures between pulsed and

continuous phonophoresis application.1 The study referenced that although the mechanical and

thermal properties may have a role in enhancing diffusion of topical agents, in this case NSAIDs,

it is inconclusive as to which method of delivery, pulsed or continuous ultrasound, is more

effective in reducing pain and increasing knee function.1

III. CONCLUSION

Based on the literature reviewed, phonophoresis paired with NSAIDs is an appropriate

modality for use in older women with knee osteoarthritis to reduce pain and increase function.

Phonophoresis would be best used for individuals with increased risk of adverse side effects of

oral NSAIDs, such as gastrointestinal discomfort. This research cannot be generalized to men or

younger populations since there was an insubstantial number of participants (less than five per

study on average) included in the literature reviewed. It should be noted that phonophoresis

ought to be done with the use of a gel-based medium instead of a cream-based topical agent, as it

has been found to be more effective. Also based on the literature, either pulsed or continuous

current can be used to drive the medication into the target tissue, as there was no difference

found in overall outcome of treatments. The major difference between pulsed and direct current

continuous US is the heating effect it will give the patient; this should be considered when

choosing between the two if a patient is known to have increased sensitivity to heat modalities.

In addition to phonophoresis, there are other ways to effectively reduce pain and increase

function for knee osteoarthritis such as iontophoresis, exercise, heat/cold, electrical stimulation,

and other therapeutic techniques. When evaluating a patient, it is important for the physical
therapist to assess contraindications for these modalities and choose which is best for his or her

patient. Based on the literature reviewed, it can be concluded that phonophoresis of topical

NSAIDs is among the modalities useful in the treatment of knee osteoarthritis symptoms. In

most research reviewed, phonophoresis was coupled with additional modalities or exercise to

further reduce pain and return function, making this research clinically applicable.

Since knee osteoarthritis is not a curable disease, phonophoresis will be used to decrease

pain and increase function (slowing the progression of the disease). Phonophoresis is an option

for long-term intervention for pain management, although there is minimal research on long-term

effectiveness. To confidently conclude that phonophoresis of topical NSAIDs is applicable in

long-term use would require research to be done on possible side effects from prolonged use, as

well as the duration of treatment effects. This research can be compared to the long-term

outcome of oral NSAID use. Additionally, there may be variability in commitment to long-term

treatment for patients. It may be more convenient for patients to take an oral NSAID for long-

term osteoarthritis pain management.

IV. REFERENCES

1. Deniz, Saadet, Topuz, Oya, Atalay, Nilgun Simsir, et al. Comparison of the Effectiveness

of Pulsed and Continuous Diclofenac Phonophoresis in Treatment of Knee Osteoarthritis.

Journal of Physical Therapy Science. 2009;21(4):331-336. doi:10.1589/jpts.21.331

2. Akinbo S, Owoeye O, Adesegun S. Comparison of the Therapeutic Efficacy of

Diclofenac Sodium and Methyl Salicylate Phonophoresis in the Management of Knee

Osteoarthritis. Turkish Journal Of Rheumatology. 2011;26(2):111-119.

doi:10.5606/tjr.2011.017

3. Michlovitz SL, Bellew JW, Nolan TP. Michlovitz's Modalities for Therapeutic

Intervention. 6th ed. Philidelphia, PA: F.A. Davis Company; 2016.

4. Boonhong J, Suntornpiyapan P, Piriyajarukul A. Ultrasound combined transcutaneous

electrical nerve stimulation (UltraTENS) versus phonophoresis of piroxicam (PhP) in

symptomatic knee osteoarthritis: A randomized double-blind, controlled trial. Journal of

Back and Musculoskeletal Rehabilitation. 2018;31(3):507-513. doi:10.3233/bmr-150492.

5. Benlidayi IC, Gokcen N, Basaran S. Comparative short-term effectiveness of ibuprofen

gel and cream phonophoresis in patients with knee osteoarthritis. Rheumatology

International. 2018;38(10):1927-1932. doi:10.1007/s00296-018-4099-9.

6. Luksurapan W, Boonhong J. Effects of Phonophoresis of Piroxicam and Ultrasound on

Symptomatic Knee Osteoarthritis. Archives of Physical Medicine and Rehabilitation.

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