Effects of Short Wave Diathermy Added on Dextrose Prolotherapy Injections in Osteoarthritis of the Knee

Abstract

Objective:

To show the effects of short wave diathermy (SWD) added on prolotherapy injections in osteoarthritis (OA) of the knee on pain, physical functioning, and quality of life.

Design:

This is a single-blinded randomized controlled study.

Setting:

Physical Medicine and Rehabilitation Department of a university hospital.

Subjects:

Sixty-three patients with OA of the knee with Kellgren–Lawrence class 2 or 3 were included in the study.

Methods:

Patients were randomized into two groups, first being dextrose prolotherapy+SWD and the second being dextrose prolotherapy with sham SWD. Patients were injected with dextrose prolotherapy solutions in the beginning, third, and sixth week of the study, for a total of three times, and took 20 min of SWD after injection (true or sham).

Outcome measures:

Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analogue Scale (VAS) for pain, and Short Form Health Survey (SF-36) were applied before, after (sixth week), and at the third month of treatment.

Results:

Both groups showed improvements in VAS, WOMAC, and SF-36 scores (p < 0.05). Between-group analyses showed no significant differences (p > 0.05).

Conclusions:

This study shows that prolotherapy is effective for pain, functionality, and quality of life in patients with OA of the knee. The effects of additional SWD require more evidence. More studies of higher quality are required to make a statement.

Introduction

Osteoarthritis (OA) is a disease that affects the articular cartilage, capsule, synovial membrane, and surrounding ligaments and muscles.¹ Symptomatic OA of the knee is known to have a prevalence of 6%–19% in patients >45 years.²

Due to the restrictions it brings to the activities of daily living of suffering patients, it has always been a focus of research and newer therapeutic options are being studied.³ Prolotherapy is one of the alternative therapeutic options that can be used in the management of OA of the knee.⁴ The basis of prolotherapy is injections of proliferative and irritant solutions to the targeted areas of the body, mostly the injured tendons, ligaments, or joints.⁵ Injection of such substances initiates inflammation that results in a response of regenerative process, governed by growth factors and cytokines in tendons and areas of enthesis.⁶ It has also been found to be effective in the management of OA of the knee in meta-analyses and reviews.^7

–10

Short wave diathermy (SWD) is a physical therapy agent that is commonly used for OA. Mechanism of SWD producing heat in deep tissues is attributed to the energy conversion of high frequency electromagnetic waves of 10–100 MHz.¹¹ Local heat in the tissues to temperatures of 40°C–45°C leads to the release of histamines and prostaglandins, increased membrane permeability, and leukocyte migration, which results in an increase in inflammatory process.¹¹

The hypothesis in this study is that SWD added on prolotherapy might lead to an increased inflammation that can help a better regeneration in injured tissues. Thus, this study is designed to assess whether SWD added on prolotherapy can improve pain, stiffness, disability, and quality of life in patients with OA of the knee.

Materials and Methods

Patients and study design

This study is approved by the local ethical commitee, and written informed consent forms were obtained from all participants. Sixty-three patients were recruited into the study between February and August 2018 (Fig. 1). Patients 45–75 years old who reported a knee pain lasting 3 months or longer and had a recent radiograph (<1 year) of the knee compatible with Kellgren–Lawrence (K-L) class 2 or 3 OA were included in this study.¹² Patients using analgesics other than acetaminophen, having pregnancy, diabetes mellitus, infectious or inflammatory arthritis, hemophilia, knee prosthesis, history of knee injections in last 3 months or anticoagulant use, allergy to ingredients of the solutions, having cardiac pacemaker or other device, or metallic implants were exluded from the study.

FIG. 1.

Flow chart of the study.

After recruitment, patients were randomized into two groups depending on their patient number, with odd numbers being recruited to SWD group, and even numbers recruited to sham SWD group. The first group took prolotherapy injections and additional SWD and the second group took prolotherapy with sham SWD.

Interventions

Prolotherapy solutions were injected to the knee by a blinded expert physician in the research team who had been using prolotherapy for >5 years and performing intra-articular and periarticular injections for >15 years, using a 25-gauge needle, with solutions being 6 mL of 25% dextrose (3 mL of 20% dextrose +3 mL of 30% dextrose) for intra-articular, and 20 mL of 15% dextrose (10 mL of 0.9% NaCl +10 mL of 30% dextrose) for periarticular. Injection points were defined as medial collateral ligamenst, adhesion points of quadriceps tendon, adhesion points of patellar tendon, tuberositas tibia, pes anserinus, lateral collateral ligaments, coronal ligaments, and medial and lateral tibia plateaus. Patients were blinded to their treatment groups.

The SWD group took short wave diathermy with specifications of 400 watt power output, 27.12 MHz frequency, 11.06 m wave length, and using condensators and electrodes of 12 cm diameter parallel to the knee for 20 min (Curapuls 970 SWD device; Enraf-Nonius). The sham SWD group took the same duration of SWD therapy with device open but not working, therefore, not emitting any kinds of electromagnetic waves, while still having the lights on. Both groups took injections in the beginning of the therapy, third week, and sixth week, a total of three times. SWD or sham SWD therapy was given right after the injections, also for a total of three times. Each group also took a home exercise program consisting of quadriceps strengthening and range of motion, six times a week for 6 weeks, each session being 40 min. Patients were also advised not to take any other analgesic drug than acetaminophen since the nonsteroidal anti-inflammatory drugs could interfere with the results of the therapy, due to their mechanism of effect.

Patients were evaluated with the outcome measures at baseline, after therapy (sixth week), and third month after the therapy.

Outcome measures

The patients were evaluated before the treatment, at the end of the treatment and at the third month after the end of the treatment with those mentioned outcome measurements.

History of demographic information and clinical properties (e.g., duration of pain and comorbidities) of the disease of patients was taken.

Visual Analogue Scale (for the intensity of pain)

Visual Analogue Scale (VAS) was used to assess the resting pain intensity of the subjects. Patients were asked to show their intensity of pain on a 10 cm long line, with 0 end being no pain and 10 cm end being highest amount of pain possible. The distance between the mark and the 0 end was measured and the result was recorded as milimeters.

Western Ontario and McMaster Universities Osteoarthritis Index

Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is an index for the assessment of OA consisting of 24 questions, with subscales being pain (5 questions), stiffness (2 questions), and physical functioning (17 questions). Test is expressed as a likert type scale, ranging from 0 to 4, with greater numbers expressing higher severity. The greater scores are associated with more severe disease.¹³

Short Form-36

Short Form-36 (SF-36) is an index for the evaluation of quality of life in a broad range of patients. It consists of eight domains: physical function, bodily pain, role-physical, general health, vitality, social function, role-emotional, and mental health. Each domain is expressed separately, rather than a total score. All of the domains are given from 0 to 100 points, with greater values being associated with a better quality of life.¹⁴

Frequencies of analgesic ingestion were also recorded for each patient. Patients were given a printed calendar, and whenever they felt the need to take an analgesic containing only acetaminophen, they were asked to write it on the calendar. The analgesic calendar was checked by researchers in each visit.

Statistical analysis

Variables were analyzed with SPSS 24.0 (IBM Corparation, Armonk, NY) and PAST 3¹⁵ programs.

Shapiro–Wilk was used to assess the normality of the distributions of single variable data, whereas Mardia (Dornik and Hansen Omnibus) test was ued for multiple variable data. Homogenity of variances was assessed with Levene test. Independent samples t-test bootstrap was used to compare independent groups, and Mann–Whitney U test was used with the Monte Carlo simulation technique.

Interaction of repeated measures between groups was analyzed with General Linear Model-Repeated ANOVA test and Friedman's two-way test, and post hoc analyses were conducted with Dunn's test and Fisher's Least Significant Difference test.

Comparison of groups for categorical variables was done with Fisher's Exact test and Fisher–Freeman–Holton test, and Monte Carlo simulation technique. Numeric data were expressed as mean ± standard deviation and median (min−max), and categorical data were expressed as n (%).

Ninety-five percent confidence interval was chosen for the analyses and p-values smaller than 0.05 were deemed significant.

Results

A total of 86 patients were included in this study. Four patients did not meet the inclusion criteria, whereas six patients refused to participate. According to randomization protocols, 37 patients were assigned to the SWD group, whereas 39 were assigned to the sham SWD group. Thirteen patients left the study, six from the SWD group and seven from the sham SWD group. In the end of the study, 31 patients were in the first group, whereas 32 patients were in the second group, thus making the study end with 63 patients in total (Fig. 1).

Demographical data of the patients are given in Table 1. There were no significant differences between the two groups when they were compared with age, gender, disease duration, body mass index, educational status, and K-L classification (p > 0.05).

Table 1.

Comparison of Demographic Data Between Groups (Group 1: Short Wave Diathermy Group, Group 2: Control Group)

	Group 1 (n = 31), mean ± SD (min./max.)	Group 2 (n = 32), mean ± SD (min./max.)	Total (n = 63), mean ± SD (min./max.)	p
Age	62.78 ± 7.53 (51/79)	58.68 ± 8.15 (37/77)	60.85 ± 7.65 (37/79)	0.308
Gender, n (%)
Female	17 (54.84)	19 (59.38)	36 (57.15)	0.589
Male	14 (45.16)	13 (40.62)	27 (42.85)
BMI, n (%)
Normal (20–25)	7 (22.7)	6 (18.8)	13 (20.67)	0.495
Overweight (25–30)	11 (35.4)	10 (31.2)	21 (33.3)
Obese (>30)	13 (41.9)	16 (50)	29 (46.03)
Marital status
Married	24 (77.41)	27 (87.09)	51 (80.95)	0.374
Single	7 (22.59)	5 (12.91)	12 (19.055)
Educational status
Illiterate	3 (5.6)	2 (6.25)	5 (7.93)	0.184
Elementary	18 (61.1)	19 (59.37)	37 (58.73)
High school	4 (11.1)	8 (25)	12 (19.04)
University	6 (22.2)	3 (9.37)	9 (14.28)
Affected side
Right	6 (19.35)	10 (31.25)	16 (25.39)	0.265
Left	8 (25.80)	6 (18.75)	14 (22.22)
Both	17 (54.83)	16 (50)	33 (52.38)
Kellgren–Lawrence Grade
2	16 (51.61)	17 (53.12)	33 (52.38)	0.805
3	15 (48.38)	15 (46.87)	30 (47.61)
Disease duration, median (min./max.)	44 (6/180)	52 (10/144)	48 (6/180)	0.506

Independent samples t-test (Bootstrap)/Fisher Exact Test (Exact)/Fisher Freeman Halton Test (Monte Carlo)/Mann–Whitney U test (Monte Carlo).

BMI, body mass index; Max., maximum; Min., minimum; SD, standard deviation.

In-group and between-group differences

Comparison of VAS and WOMAC scales between groups and before and after treatment is summarized in Table 2, and comparison of SF-36 scales between groups and before and after treatment is summarized in Table 3.

Table 2.

Comparison of Visual Analogue Scale and WOMAC Scores in Groups and Between Groups (Group 1: Short Wave Diathermy Group, Group 2: Control Group)

	Group 1, n = 31	Group 2, n = 32	p1	p2	p3	p4, p5, p6, p7
VAS
Before, mean ± SD	8.24 ± 0.97	8.37 ± 1.28	0.732	0.272	0.241	<0.001
After (week 6), mean ± SD	3.56 ± 1.66	4.37 ± 2.17	0.211
Month 3, mean ± SD	4.01 ± 2.34	3.97 ± 1.92	0.949
WOMAC-P
Before, mean ± SD	13.14 ± 3.39	13.85 ± 4.69	0.578	0.954	0.274	<0.001
After (week 6), mean ± SD	6.59 ± 4.29	7.72 ± 4.42	0.426
Month 3, mean ± SD	6.65 ± 3.45	8.82 ± 4.50	0.115

General Linear Model Repeated ANOVA (Wilks' Lambda)—post hoc test: Fisher's LSD/Mann–Whitney U test/Friedman test—post hoc test: Dunn's test.

med [min−max]: median.

p1: p-values for between-group comparisons.

p2: After treatment versus month 3 comparison for group 1.

p3: After treatment versus month 3 comparison for group 2.

p4: Before treatment versus after treatment comparison for group 1.

p5: Before treatment versus month 3 comparison for group 1.

p6: Before treatment versus after treatment comparison for group 2.

p7: Before treatment versus month 3 comparison for group 2.

p < 0.05 statistically significant.

LSD, least significant difference; VAS, Visual Analogous Scale; WOMAC-P, Western Ontario and McMaster Universities Osteoarthritis Index-Pain.

Table 3.

Comparison of SF-36 Scores in Groups and Between Groups (Group 1: Short Wave Diathermy Group, Group 2: Control Group)

	Group 1, n = 31	Group 2, n = 32	p1	p2	p3	p4, p5, p6, p7
SF-36 PF
Before, mean ± SD	50.17 ± 19.13	36.37 ± 20.92	0.101	0.727	0.511	<0.001
After (week 6), mean ± SD	63.44 ± 12.74	59.32 ± 21.41	0.456
Month 3, mean ± SD	64.83 ± 11.08	61.79 ± 21.54	0.596
SF-36 PR
Before, mean ± SD	25 (0/100)	0 (0/100)	0.088	0.340	1	0.001
After (week 6), mean ± SD	75 (0/100)	50 (0/100)	0.301
Month 3, mean ± SD	50 (0/100)	67 (0/100)	0.623
SF-36 ER
Before, mean ± SD	36.94 ± 32.19	36.68 ± 24.68	0.969	0.168	0.988	0.001
After (week 6), mean ± SD	65.78 ± 30.59	54.32 ± 24.94	0.244
Month 3, mean ± SD	56.61 ± 15.58	54.42 ± 24.92	0.752
SF-36 V
Before, mean ± SD	50 (30/70)	45 (20/75)	0.151	0.171	0.086	0.001
After (week 6), mean ± SD	60 (15/75)	55 (15/65)	0.406
Month 3, mean ± SD	60 (30/65)	55 (40/65)	0.731
SF-36 MH
Before, mean ± SD	64.61 ± 16.35	51.37 ± 20.84	0.153	0.101	0.808	0.005
After (week 6), mean ± SD	71.56 ± 10.26	65.74 ± 19.44	0.255
Month 3, mean ± SD	73.11 ± 11.38	66.58 ± 15.13	0.149
SF-36 GH
Before, mean ± SD	51.61 ± 14.17	43.16 ± 22.68	0.186	0.258	0.349	0.001
After (week 6), mean ± SD	63.50 ± 14.01	54.42 ± 21.55	0.138
Month 3, mean ± SD	60.22 ± 12.85	57.47 ± 16.60	0.564
SF-36 P
Before, mean ± SD	40.89 ± 22.78	35.37 ± 29.52	0.550	0.630	0.309	0.001
After (week 6), mean ± SD	64.61 ± 16.94	61.32 ± 24.41	0.638
Month 3, mean ± SD	61.94 ± 19.80	67.00 ± 23.13	0.469
SF-36 SF
Before, mean ± SD	57.17 ± 18.87	47.53 ± 25.84	0.180	0.681	0.369	0.001
After (week 6), mean ± SD	75.89 ± 20.85	67.21 ± 31.25	0.325
Month 3, mean ± SD	73.89 ± 12.76	73.84 ± 19.06	0.995

General Linear Model Repeated ANOVA (Wilks' Lambda)—post hoc test: Fisher's LSD/Mann–Whitney U test/Friedman test—post hoc test: Dunn's test.

med [min−max]: median [minimum−maximum].

p1: p-values for between-group comparisons.

p2: After treatment versus month 3 comparison for group 1.

p3: After treatment versus month 3 comparison for group 2.

p4: Before treatment versus after treatment comparison for group 1.

p5: Before treatment versus month 3 comparison for group 1.

p6: Before treatment versus after treatment comparison for group 2.

p7: Before treatment versus month 3 comparison for group 2.

p < 0.05 statistically significant.

ER, emotional role; GH, general health; PF, physical functioning; PR, physical role; MH, mental health; P, bodily pain; SF, social role functioning; SF-36, Short Form-36; V, vitality.

VAS, WOMAC-A, WOMAC-S, WOMAC-F, and WOMAC-total values showed improvements in within-group analyses conducted between initial values and latter values, namely after treatment and third month (p < 0.001), whereas differences between after treatment and third month values were insignificant. Between-group analyses showed no significant differences (Table 3).

Discussion

This study shows that prolotherapy is effective for pain, functionality, and quality of life in patients with OA, and these effects carry on in the longer term. SWD added on prolotherapy did not show any additional beneficial effect.

To prevent the financial burden and complications that may occur as a result of surgery in knee osteartritis, there are ongoing studies for new treatment options that will reverse the progressive structure of the knee or stop the progression of the damage. Regenerative therapies are particularly important for the recovery of damaged joint tissues and periarticular structures.¹⁶ Recently, dextrose prolotherapy is getting more popular as a type of regenerative therapy. This method of management has been getting more evidence in the form of meta-analyses and reviews.^7
–9 Although number of the studies is getting higher, the use of prolotherapy in OA lacks a consensus in the concentration, number of injections, doses, or intervals. Former studies used dextrose doses ranging from 10% to 30%, both intra-articular and periarticular.¹⁷ Thus, it was decided to use periarticular 15% dextrose and intra-articular 25% dextrose in this study. Another meta-analysis evaluating the use of dextrose prolotherapy reported studies using dose intervals ranging from 2 to 6 weeks, particularly in degenerative conditions.¹⁸ Thus, the study was conducted with injections done every 3 weeks, which was reported to be enough for the effects induced by prolotherapy.¹⁸

Four studies of 258 patients were included in a meta-analysis evaluating prolotherapy from knee OA up to 2015.⁷ These studies compared efficacy of prolotherapy injections to either 0.9% saline or exercise programs. Studies included in that meta-analyses had follow-up times ranging from 5 weeks to a year, and their results were compatible with the preservation of effects in the long term. It is also claimed that further evidence is required for the effects of prolotherapy, as well as its comparison with other therapies including exercises or methods other than injections. Another review studying the effects of prolotherapy included 10 studies with a total of 549 patients with knee OA.⁸ Similar to the meta-analysis by Sit et al., this review also found that prolotherapy provided improvement in WOMAC and VAS scores, with beneficial effects being kept both in short term (4 weeks) and in long term (2.5 years). A review examined 10 studies investigating prolotherapy and biological injection therapies (platelet-rich plasma, mesenchymal stem cell therapy, and growth factors) in OA, and stated that prolotherapy had moderate quality evidence for improvements in WOMAC scores, VAS scores, and patient satisfaction.⁹ Another review published in 2017 stated that low-level laser therapy added on prolotherapy could increase fibroblast proliferation, lower pain levels, and improve healing.¹⁹ It was decided to use SWD as a therapeutic agent without injection, which could potentially increase inflammation and improve healing, and investigate whether it had additional effects on prolotherapy.

Hypertonic dextrose solutions are osmotic shock agents that cause dehydration and lysis in cells inside tissues. This local traumatic event triggers granulocyte and macrophage activation. Resulting inflammation causes fibroblast stimulation and the release of growth factors help in tissue regeneration.^4,6 SWD has a thermal effect on tissues, resulting in vasodilation as well as inflammation, which may also contribute to regeneration.²⁰ Inflammation as a result of tissue injury happens in a fairly short duration.²¹ Thus, the authors proposed that SWD added on prolotherapy might have aggravated inflammation, and resulting effects could have been seen more robustly. Beneficial effects of SWD in OA of the knee has been shown in earlier studies.^11,22 A study conducted in 2012 showed that SWD has an immediate effect on a knee with OA.¹¹ Therefore, the authors chose to apply SWD right after prolotherapy injections. The lack of additional benefits may be attributed to the lack of precisely defined protocols for the management of OA.¹¹

As a novel point when compared with the former studies, the authors have investigated whether dextrose prolotherapy contributes to a better quality of life in patients with OA.^7,8 Both groups have shown improvements in WOMAC scores as well as quality of life scales. This improvement is attributed to the alleviation of the pain and patient satisfaction.

Both groups took isometric muscle strengthening as a home program. Dumais et al. reported that knee exercises added to prolotherapy injections showed better improvements in functionality when evaluated with WOMAC.²³

No adverse effects were observed in this study besides pain while having injections in any of the interventions.

Limitations of the study were the brief follow-up time, single blind design, limited amount of SWD sessions, and no groups without any kind of therapy. Since there are no defined protocols for effectivity of SWD therapy, the authors decided to investigate just one session after the injection since th goal was to show whether it would augment the effects of the injection. Although inclusion of a group who took only routine care (exercise/physical therapy) and sham injections would be helpful to show the effectiveness of prolotherapy injections, the goal of the study was to show whether an addition of SWD would be helpful in augmenting the effects of prolotherapy. Thus, such a group was not included in the study. Lack of local anesthetics was another limitation of the study. Although addition of an amide local anesthetic would be helpful in management of pain with injections, this is not an integral part for the effectiveness of prolotherapy. The participants in the study showed improvements in their overall pain levels after prolotherapy injections, even without local anesthetics. Although these improvements seem to be attributable to prolotherapy injections based on former controlled studies,^17,18 it is not possible to clearly attribute this effect to the injections since this study did not include a sham injection group, due to the goal of the study. The study design was also chosen as a single blind study. A study including double-blind design, cross-over between groups, waiting list, or saline injection groups could have resulted in clearer statements.

Although SWD was not shown to be useful in the management of knee OA after prolotherapy injections, it is still not clear whether multiple sessions of SWD would still have a limited use with prolotherapy injections. It is advisable to conduct more studies using multiple sessions of SWD of better design as stated to draw a conclusion in concommitant use of prolotherapy and SWD.

Conclusion

Prolotherapy was shown to be effective for pain, functionality, and quality of life in patients with OA of the knee. Although it was not shown that SWD has additional benefits when combined, it requires more evidence to make a statement. More studies of higher quality are required that includes prolotherapy versus other therapeutic options with more patients, and with a standardized injection protocol.

Footnotes

Acknowledgments

None of the authors, their immediate families, and any research foundation with which they are affiliated received any financial payments or other benefits from any commercial entity related to the subject of this article.

All patients gave written informed consent for involvement in the study.

This study was approved by board of ethics in İzmir Kâtip Çelebi University, Ataturk Research and Training Hospital.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

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