566618

research-article2015
TAB0010.1177/1759720X14566618Therapeutic Advances in Musculoskeletal DiseaseF Eslamian and B Amouzandeh

Therapeutic Advances in Musculoskeletal Disease Original Research

Therapeutic effects of prolotherapy with

Ther Adv Musculoskel Dis

2015, Vol. 7(2) 35­–44

intra-articular dextrose injection in patients DOI: 10.1177/

1759720X14566618

with moderate knee osteoarthritis: a single-

© The Author(s), 2015.
Reprints and permissions:
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arm study with 6 months follow up

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Fariba Eslamian and Bahman Amouzandeh

Abstract
Objectives: Prolotherapy is an injection-based complementary treatment, which has shown
promising results in the treatment of different musculoskeletal disorders. The aim of this
study was to determine the therapeutic efficacy of dextrose prolotherapy on pain, range of
motion, and function in patients with knee osteoarthritis (OA).
Methods: In this single-arm prospective study, participants with symptomatic moderate knee
osteoarthritis underwent prolotherapy with intra-articular injection of 20% dextrose water at
baseline, and at 4 weeks and 8 weeks later. Patients were followed for 24 weeks. Pain severity
at rest and activity, according to the visual analog scale (VAS), articular range of motion
(ROM), and Western Ontario and McMaster Universities arthritis index (WOMAC) scores were
measured at baseline, 4, 8, and 24 weeks later.
Results: A total of 24 female patients (average age: 58.37 ± 11.8 years old) received 3-monthly
injection therapies. Before the treatment, the mean articular range of motion was 105.41 ±
11.22°. Mean VAS scale at rest and activity was 8.83 ± 1.37 and 9.37 ± 1.31, respectively. At
the end of week 24, knee ROM increased by 8°. Pain severity in rest and activity decreased
to 4.87 ± 1.39, 45.86%, and 44.23%, respectively (p < 0.001). Total WOMAC score and its
subcategories showed a continuous improvement trend in all the evaluation sessions, so that
at the end of the study, the total score decreased by 30.5 ± 14.27 points (49.58%)
(p < 0.001). Improvements of all parameters were considerable until week 8, and were
maintained throughout the study period.
Conclusions: Prolotherapy with three intra-articular injections of hypertonic dextrose given
4 weeks apart for selected patients with knee OA, resulted in significant improvement of
validated pain, ROM, and WOMAC-based function scores, when baseline levels were compared
at 24 weeks. Further studies with randomized controlled trials involving a comparison group
are suggested to confirm these findings.

Keywords:  dextrose prolotherapy, intra-articular injection, knee osteoarthritis, prolotherapy

Correspondence to:
Fariba Eslamian, MD
Physical Medicine and
Rehabilitation Research
Center, Tabriz University
of Medical Sciences, Imam
Introduction 2012; Felson, 2005; Hochberg et  al. 1996]. Reza Hospital, Golgasht
Ave, Tabriz, 5166615556,
Osteoarthritis (OA) is an age-dependent disease Considering the nature of the mechanical pres- Iran
caused by degenerative and healing processes in sure applied on the knee joint, it is a common eslamiyanf@tbzmed.ac.ir
Bahman Amouzandeh, MD
subchondral tissue of articular and bone cartilage, joint for OA [Gupta et al. 2005; Felson, 2003]. Physical Medicine and
resulting in an alteration of its biomechanical Rehabilitation Department,
Tabriz University of
properties that eventually causes pain, stiffness, There are few treatment methods for moderate to Medical Sciences, Tabriz,
and decreased articular function [Hochberg et al. severe OA; most focus on relieving the symptoms Iran

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Therapeutic Advances in Musculoskeletal Disease 7(2)

but do little to change the biochemical environ- American Rheumatological Association [Toledo
ment of the joint or on the disease process. et al. 2011; Altman, 1991], who met the inclusion
Current therapies include simple analgesics, anti- and exclusion criteria, were recruited from physi-
inflammatory drugs, muscle strengthening exer- cal medicine and rehabilitation clinics at Imam
cises, physical therapy, intra-articular injection of Reza Hospital, Tabriz University of Medical
cartilage supplements such as hyaluronic acid Sciences. We treated eligible patients and followed
agents, arthroscopic surgery, and arthroplasty their status from July 2012 to November 2013.
[Michael et  al. 2010; Toopchizadeh et  al. 2012;
Barron and Rubin, 2007], nevertheless no non- The inclusion criteria were patients aged 45 –75
surgical treatment is uniformly effective. years old who had: (a) moderate or moderate to
severe knee OA (grade II or III according to the
Prolotherapy, also known as proliferative therapy, or radiological classification of knee OA defined by
regeneration injection therapy, is a complementary Kellgren and Lawrence [Toledo et al. 2011]); (b)
injection treatment for musculoskeletal pains. lack of any inflammatory or rheumatologic dis-
Hypertonic dextrose is the most commonly injected eases such as rheumatoid arthritis; (c) intractable
solution. Although the mechanism of this treatment pain and joint tenderness refractory to conserva-
modality is not clearly understood, it is hypothesized tive treatment; (d) no response to medications or
that the solution creates a host inflammatory response physiotherapy in the last 3 months; (e) consent to
through the upgrading of chemical mediators, which participate in the study.
results in stronger connective tissue, improved bio-
mechanics, and joint function and soft tissue recovery The exclusion criteria were patients who had: (a)
[Jensen et al. 2008; Rabago et al. 2005]. severe OA (grade IV according to the Kellgren–
Lawrence system of classification); (b) history of
Several reports have revealed the effects of dex- rheumatologic or inflammatory diseases; (c)
trose prolotherapy in treating refractory musculo- received oral or systemic corticosteroids during
skeletal disorders such as low back pain, tendonitis, the 2 weeks prior to treatment; (d) received an
lateral epicondylitis, and ligament damage intra-articular injection of hyaluronic acid agents
[Rabago et al. 2005;Yelland et al. 2003; Klein et al. during the previous month; (e) poorly controlled
1993]. Though prolotherapy has been used for diabetes mellitus with fasting blood sugar greater
knee OA for many decades, only recently has the than 11.1 mmol/L; (f) history of anticoagulation
efficacy of the results been studied [Hauser and therapy; (g) history of prior total knee replace-
Hauser, 2007; Rabago et al. 2012]. On the other ment surgery.
hand, experimental data in this area are rather
controversial and there is no general consensus The radiological criteria of knee joint OA severi-
about its application in joint degenerative diseases ties used in this study were based on the Kellgren–
[Hashemi et al. 2010; Rabago et al. 2010]. Lawrence classification: grade 0: normal; grade I:
small osteophytes without clinical importance;
It should be noted that the number of elderly peo- grade II: definite osteophytes but normal joint
ple in society is increasing and musculoskeletal space; grade III: definite osteophytes with moder-
disorders, mainly OA in this population, are very ate narrowing of joint space; grade IV: definite
common. Routine treatments for pain and disa- osteophytes with severe narrowing of joint space.
bility in these patients have low efficacy, and some
treatments, including hyaluronic acid injection
therapy, have high costs. It is possible that prolo- Research ethics
therapy has acceptable effects on OA in these The study procedure was in accordance with the
patients. Therefore, we designed this study to ethical standards of the responsible local commit-
investigate the effectiveness of dextrose prolother- tee on human experimentation of Tabriz
apy in decreasing pain, improving daily functional University of Medical Sciences and it was
ability, and increasing the joint range of motion approved by this ethics committee. The study
(ROM) in patients with knee OA. protocol was also registered as a clinical trial in
the Iranian Registry of Clinical Trials (www.irct.
ir, number 201210213217 N4).
Methods and materials
In this single-arm trial, adult patients diagnosed Before participating in the project, the aims of the
with knee OA based on the clinical criteria of the study were explained orally to all the patients and

36 http://tab.sagepub.com
 F Eslamian and B Amouzandeh

written informed consents were obtained from all (most severe), 20, 8, and 68, respectively. Higher
study participants. scores indicate greater disease severity
[McConnell et al. 2001; Bellamy et al. 1988]. The
WOMAC scale has been validated for use with
Intervention Iranian patients [Nadrian et al. 2012].
Each patient received three intra-articular injec-
tions at 1-month intervals in weeks 0, 4, and 8. The participants were recommended to take
During the procedure, each patient was placed in acetaminophen 500 mg as needed and were
a supine position with the knee flexed at 10–15°, advised not to use nonsteroidal anti-inflamma-
and the intra-articular injection landmark was tory drugs during the following 2 weeks because
determined below the superolateral part of the of their inhibitory effects on the recovery process.
patella [Lento et al. 2011]. The injection site was They were also discouraged from taking physical
located by a lateral approach; in patients without therapy during the 6-month follow-up period
sufficient space on the lateral side, a medial because of its confounding effect on evaluating
approach was performed. Under sterile condi- research in our essential treatment. The patients
tions, a composition of 8 ml of 20% dextrose and were not discouraged or prevented from using
2 ml of 1% lidocaine was injected by an expert other medications prescribed for their underlying
physiatrist using a 22 gauge needle. systemic diseases.

Outcome measures Data analysis

Baseline demographic findings and Western Baseline data are reported as means ± standard
Ontario and McMaster Universities arthritis deviation (continuous data), or percentages and
index (WOMAC) values, knee ROM, and pain numbers (categorical data), depending on the
severity at rest (seated) and in activity (after walk- data level. The mean changes at each level were
ing 6 m) using the visual analogue scale (VAS) calculated by comparing the weekly value and
were recorded. The patients were evaluated for the baseline value as follows: mean (week n
these parameters at the time of first injection, and score - week 0 or baseline score). The improve-
4, 8, and 24 weeks later. ment percentage is calculated by dividing the
amount of change from baseline at each level on
Knee ROM in flexion was determined in prone the maximum expected change (baseline score
position using an international standard 360º - week n score/ baseline score), and multiplying
goniometer. The validity and reliability of this it by 100.
measuring device has been demonstrated by other
researchers [Brosseau et  al. 2001; Kolber et  al. Achievement of minimal clinical difference with
2012]. regard to similar studies was calculated as 20%
for total WOMAC score and 50% for overall
Pain was measured using a 10 cm VAS. Pain improvement in this score. Repeated measures
intensity is classified using a range from 0 to 10, analysis of variance (ANOVA) was used to evalu-
in which 0 = no pain at all and 10 = the worst ate the serial changes of different variables during
possible pain. Patients were asked to sign the the treatment period. All data were analyzed using
place on the VAS scale that corresponded to their the Statistical Package for Social Sciences, version
pain level. 16.0; p < 0.05 was considered to be statistically
significant.
The WOMAC questionnaire is used to evaluate a
patient’s functions when diagnosed with rheu-
matic diseases, especially knee OA. The WOMAC Results
is a 24-item questionnaire with three subscales In this study, during a 16-month period, 24
measuring pain (five items), stiffness (two items), female patients with moderate and moderately
and physical function (17 items). Answers to each severe knee OA were enrolled, treated, and
of the 24 questions are scored on five-point Likert followed.
scales (none = 0, slight = 1, moderate = 2, severe
= 3, extreme = 4), with total scores ranging from At baseline, of the 33 patients in the first screening,
0 to 96. So, the maximum possible scores for two patients were excluded because of poorly con-
WOMAC, pain, stiffness, and function are 96 trolled diabetes mellitus and three other patients

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Therapeutic Advances in Musculoskeletal Disease 7(2)

Patients enrolled initially according

to inclusion criteria
n = 33

Exclusion from the study:

two patients for insulin-dependent
diabetes mellitus and three
patients declined participation

Initial examination and first assessment by WOMAC and

VAS questionnaires and goniometry, first run of injection
n = 28

Drop out from the study:

two after the first injection and two after the second
injection because of injection pain and personal issues

Three intra-articular injections and continue to assess

patients until week 24
n =24

Figure 1.  Clinical trial chart. VAS, visual analog scale; WOMAC, Western Ontario and McMaster Universities
arthritis index.

declined to participate. A total of 28 patients met moderate to severe (grade III–IV), and 4 were
the criteria and were enrolled in the study, but four placed in the mild to moderate (grade I–II) OA
patients failed to complete and were excluded from grading categories. Of the eight patients with only
the analysis. These included two women who one treated knee, three were in the right knees,
dropped out because of the pain after the first injec- the remainder were in the left knees.
tion, and two men refused to continue therapy
because of personal issues after the second injection Before treatment, the mean knee ROM was
(not related to the treatment). At the end, 24 patients 105.41° ± 11.22°. Mean VAS scale at rest and
were included in the final evaluation (Figure 1). activity was 8.83 ± 1.37 and 9.37 ± 1.31, respec-
tively. At the end of week 24, mean knee ROM
The study sample consisted of female adults increased to 113.5° ± 7.22°. Pain severity, both in
(58.37 ± 11.83 years old; range: 46–72 years), a rest and activity, decreased to 4.87 ± 1.39,
majority of whom had a body mass index of 45.86% and 44.23%, respectively (p < 0.001).
26–30 kg/m2 (Table 1). The mean WOMAC total score was 58.83 ±
14.52 points, consisting of pain subscore values
A total of 16 patients had both knees treated, con- 14.37 ± 2.88, stiffness subscore values 3.25 ±
tributing 32 knees, and 8 patients had only 1 knee 2.64, and function subscore values 41.2 ± 10.35
treated. The total sample sizes for analysis for points.
WOMAC as well as pain VAS was 24, regardless
of the number of injected knees (analysis per per- Total WOMAC score and its subcategories had a
son); 40 knees were included for ROM evaluation continuous improvement trend in all the evalua-
(analysis per knee). tion sessions, so that the total score had decreased
by 30.5 ± 14.27 points (49.58%) at the end of
Of the 24 patients (40 injected knees) who com- the study (p < 0.001). More than half of the par-
pleted the study, 30 knees were placed in the ticipants achieved approximately 50% improve-
moderate (grade II–III), 6 were placed in the ment in total WOMAC score at 24 weeks.

38 http://tab.sagepub.com
 F Eslamian and B Amouzandeh

Table 1.  Baseline participants’ characteristics (n = 28, total 48 injected knees).

Variable Number (%)

Age (years) 58.37 ± 11.83
Sex 26 (92.8%) female, 2 (7.2%) male
Duration of knee pain (months) 18.5 ± 8.53
Body mass index (kg/m2 ), number (%)
< 25 3 (10.7%)
26–30 19 (67.8%)
> 31 6 (21.4%)
Previous physiotherapy per person 15 (53%)
Previous hyaluronic acid injection per knee 4 (8%)
Western Ontario and McMaster Universities arthritis index total score (0–96),
point ± SD 58.83 ± 14.52
Pain (0–20) 14.37 ± 2.88
Stiffness (0–8) 3.25 ± 2.64
Function (0–68) 41.2 ± 10.35
Resting visual analog scale (0–10), point ± SD 8.83 ± 1.37
Activity visual analog scale (0–10), point ± SD 9.37 ± 1.31
Range of motion (°) 105.41 ± 11.22
X-ray Kellgren–Lawrence osteoarthritis
severity, score (I–IV)
Grade I–II (mild–moderate) 6 (12%)
Grade II–III (moderate) 34 (70%)
Grade III–IV (moderate–severe) 8 (16%)
SD, standard deviation.

The baseline characteristics of the participants Discussion

are presented in Table 1. Changes in knee Prolotherapy has been reported as a useful
ROM, pain VAS (rest and activity), WOMAC method in the treatment of chronic musculoskel-
and its subscales during the study period and etal and joint diseases. It is proposed that prolo-
their percentage of improvement and mean therapy causes mild inflammation and cell stress
changes in each time are demonstrated in Tables in the weakened ligament or tendon area, releases
2 and 3. cytokines and growth factors, and induces a new
healing cascade in that area, which leads to activa-
Following the prolotherapy sessions, ROM, pain tion of fibroblasts, generation of collagen precur-
VAS at rest and activity, and WOMAC scales were sors, and strengthening of the connective tissue
considerably improved until week 8 and then [Rabago et al. 2012; Jensen et al. 2008]. It is also
maintained throughout the study period. It should hypothesized that in dextrose prolotherapy, the
be noted between week 8 and the last evaluation increased extracellular glucose level and the con-
at week 24, there was a lesser but still statistically tact of human cells with the hypertonic environ-
significant improvement compared with baseline ment causes an increase in multiple growth
(p < 0.001). Figures 2 and 3 show these improve- factors in different cells. By these presumed
ment trends in WOMAC total score and pain mechanisms, the hypertonic dextrose solution
severity using VAS at various periods of the study, stimulates the proliferation of chondrocytes, oste-
respectively. ocytes, and fibroblasts. These cells then excrete
extracellular matrix, which enhances the stability
During our study, no side effects including infec- of the joints by tightening and strengthening the
tion, exacerbation of inflammation, or sustained ligaments, tendons, and joint stabilizing struc-
pain related to the injection or injected fluid were tures [Rabago et  al. 2013b; Yelland et  al. 2003;
seen. Klein et al. 1993].

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Therapeutic Advances in Musculoskeletal Disease 7(2)

Table 2.  Changes in range of motion and visual analogue scale during the study periods.

Evaluation intervals variable At baseline Week 4 Week 8 Week 24 p value

  (48 injected knees) (44 injected knees) (40 injected knees) (40 injected knees)  
Range of motion (°) 105.41 ± 11.22 110.37 ± 9.7 113.08 ± 8.06 113.5 ± 7.22 *< 0.001
Percentage changes$ – (19.6%) (25.5%) (27.0%)  
Point changes‡ – 5.96 ± 5.7 7.67 ± 8.29 8.18 ± 9.31  
Rest visual analogue scale 8.83 ± 1.37 5.12 ± 2.02 4.66 ± 1.65 4.87 ± 1.39 *< 0.001
Percentage changes$ – (41.19%) (44.78%) (44.23%)  
Point changes‡ – −3.7 ± 2.19 −4.16 ± 2.18 −3.95 ± 1.57  
Activity visual analogue scale 9.37 ± 1.31 6.08 ± 1.95 5.25 ± 1.48 4.87 ± 1.39 *< 0.001
Percentage changes$ – (34.43%) (42.32%) (45.86%)  
Point changes‡ – −3.29 ± 1.92 −4.12 ± 1.82 −4.29 ± 1.39  

*p is two-sided significant (< 0.05) using repeated measures of analysis of variance statistical test.
$Improvement percentage of measured values is calculated by dividing the amount of changes at each level on the maximum of expected change

and multiplying it by 100.

‡The mean changes in each level are calculated compared with the baseline value: mean (week n score - week 0 or baseline score).

Table 3.  Changes in Western Ontario and McMaster Universities arthritis index score and its subscales during the study periods.

Evaluation intervals variable At baseline Week 4 Week 8 Week 24 p value

  (48 injected (44 injected (40 injected (40 injected  

knees) knees) knees) knees)
Total Western Ontario and McMaster 58.83 ± 14.52 36.45 ± 9.91 31 ± 7.91 28.33 ± 7.2 *< 0.001
Universities arthritis index
Percentage changes$ – (34.35%) (44.45%) (49.58%)  
Point changes‡ – −22.37 ± 14.71 −27.83 ± 14.71 −30.5 ± 14.27  
Pain 14.37 ± 2.88 9.29 ± 2.45 8.16 ± 2.37 7.54 ± 1.99 *< 0.001
Percent changes$ – (34.22%) (41.75%) (46.19%)  
Point changes‡ – −5.07 ± 2.73 −6.2 ± 3.18 −6.83 ± 3.18  
Stiffness 3.25 ± 2.64 1.7 ± 1.47 0.94 ± 0.87 0.91 ± 0.87 *< 0.001
Percentage changes$ – (37.67%) (57.42%) (58.12%)  
Point changes‡ – −2.04 ± 2.71 −2.87 ± 2.5 −2.89 ± 2.1  
Function 41.2 ± 10.35 25.95 ± 7.88 22.45 ± 5.62 20.41 ± 5.34 *< 0.001
Percentage changes$ – (32.65%) (42.25%) (47.85%)  
Point changes‡ – −15.25 ± 10.5 −18.75 ± 10.52 −20.79 ± 10.3  

*p is two-sided significant (< 0.05) using repeated measures of analysis of variance statistical test.
$Improvement percentage of measured values is calculated by dividing the amount of changes at each level to the maximum of expected change

and multiplying it by 100.

‡The mean changes in each level are calculated compared with the baseline value: mean (week n score - week 0 or baseline score).

This single-arm clinical trial found that dex- subscales following prolotherapy [Rabago et  al.
trose prolotherapy could cause significant 2012, 2013b; Hashemi et  al. 2010; Reeves and
reduction in patients’ pain at rest and during Hassanein, 2003; Kim et al. 2002].
activity, and could enhance joint ROM and
WOMAC scores. In the present study, knee flexion ROM increased
by 8° (27%) at week 24, which is the amount of
There are few reports regarding the effects of pro- minimum detectable change that is required to be
lotherapy on OA. All these studies have shown an stated with 95% certainty that the change is not
improvement in different pain scales between due to intertrial variability or measurement error
36% and 55%, as well as improved WOMAC [Kolber et al. 2012].

40 http://tab.sagepub.com
 F Eslamian and B Amouzandeh

Figure 2.  Changes of WOMAC total score at various periods of the study. WOMAC, Western Ontario and
McMaster Universities arthritis index.

Figure 3.  Changes of pain severity using the VAS score at various periods of the study. VAS, visual analog
scale.

WOMAC total score in our study improved by Similarly, Rabago and colleagues reported a
49.58% at the end of week 24 as well as 31.5% decrease in WOMAC score as well as a
46.19%, 58.12%, and 47.85% reduction in 34.7%, 24.4%, and 36.8% decrease in pain, stiff-
pain, stiffness, and function subscale scores, ness, and function subscale scores, respectively at
respectively. This improvement exceeds the the end of 52 weeks [Rabago et  al. 2012].
reported minimal clinical difference of 12–25% However, they reported less improvement in
found in related studies [Tabach et  al. 2005, WOMAC scores compared with our findings.
2009]. There is one possible explanation for this

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Therapeutic Advances in Musculoskeletal Disease 7(2)

difference: we evaluated patients for 24 weeks, dextrose prolotherapy, both in intra-articular car-
while Rabago and colleagues followed their tilage damage as well as extra-articular ligament
patients for 52 weeks. injury [Rabago et al. 2012; Reeves and Hassanein,
2000, 2003]. Accordingly, mechanical instability
Although cartilage volume increases after each due to injury or partial tearing of surrounding
prolotherapy session and will remain increased ligaments, especially the lateral collateral liga-
for a time, it decreases over time, which has a sig- ment (LCL), could be another challenging issue
nificant correlation with the pain subscales of the in patients with knee OA.
WOMAC score [Rabago et al. 2013a]. Therefore,
it is possible that with longer follow up, we would During the present study, extra-articular injection
observe similar improvements to those reported in addition to intra-articular injection was not
by others. included in the research protocol. It seems appli-
cation of a dextrose injection in the insertion-to-
As previously mentioned, the total WOMAC bone site of ligaments and tendons is more
score was considerably improved until week 8 and investigational for knee OA and is mainly indi-
then maintained throughout the study period. In cated in ligament laxity such as the anterior cruci-
other words, treatment effects reached a plateau ate ligament (intra-articular ligament) or LCL
after 8–12 weeks, similar to the results described (extra-articular ligament). In other words, the
by others [Rabago et al. 2012]. This observation first priority in our study was a focus on the dam-
could be due to the possibility of overuse of the aged cartilage and not on external ligaments or
knee after a temporary improvement in pain and tendons. However, this would be a promising
function, and ignoring the recommendations method for showing the better efficacy of prolo-
about gradual increase of pressure on the knee. therapy, especially for young or middle-aged
patients with ligament injury, and even for elderly
Other studies have also reported that the improve- patients with knee OA in whom LCL damage is
ments attenuate over time and sometimes the not uncommon. Further studies in this area are
symptoms are exacerbated after several months, necessary to draw a definitive conclusion.
which indicate the short-term effects of the treat-
ment, similar to the injections of hyaluronic acid In our study, two patients left the survey because
agents [Samson et  al. 2007]. Though post-treat- of the pain during injections. Actually one of the
ment pain is not as severe as their experienced difficulties that occurs in blind injections is pain
original pretreatment pain, this could suggest that during or after injection. This problem is mostly
these patients need several injections at intervals seen in obese participants or involved joints with
to keep the desired results. synovial hypertrophy or major osteophytes as well
as among patients with bilateral narrowing of the
Ignoring the patient’s other pain sources includ- joint space. Therefore, it is possible that an incor-
ing joint-surrounding tendons and ligaments rect location of the injected solution and conse-
could be another potential cause in this regard; quent inflammation of the surrounding tissues
we did not treat enthesopathies or the ligament are the main causes of pain during and after injec-
fibro-osseous junctions with extra-articular dex- tion, respectively. Accurate localization using
trose injections around these elements in our ultrasound-guided injection from the suprapatel-
study. So, it appears that ligaments or other struc- lar bursa seems to be an ideal choice for minimiz-
tures need to be treated to get the full benefit ing pain among such patients.
from prolotherapy.

Ligaments’ strength and integrity plays an impor- Strengths and limitations

tant role in the function and stability of the joint, We observed acceptable results on validated and
and one of the reasons for the triggering or exac- patient-oriented outcomes using prolotherapy as
erbation of OA is dysfunction of the supportive a cost-effective treatment for patients with mod-
ligaments [Reeves and Hassanein, 2003; Ongley erate or moderately severe OA who are refractory
et al. 1988]. Previous studies evaluating the prolo- to conservative therapy; however, this study had
therapy effects on OA patients with knee instabil- some limitations. The study was a single-arm trial
ity caused by injury have shown desirable results and could not define this method’s superiority
in improving pain intensity and reducing knee over other methods. The sample size in our study
instability, demonstrating the positive effects of was small and we did not include a control group

42 http://tab.sagepub.com
 F Eslamian and B Amouzandeh

to better compare the results. In addition, our for measuring maximum active knee flexion and
assessment tools were mostly self reported and extension of patients with knee restrictions. Arch Phys
subjective, hence, more assessments such as artic- Med Rehabil 82: 396–402.
ular cartilage thickness measurement by imaging Felson, D. (2005) The sources of pain in knee
techniques or musculoskeletal ultrasonography osteoarthritis. Curr Opin Rheumatol 5: 624–628.
are recommended for objective confirmation of
Felson, D. (2003) Epidemiology of osteoarthritis. In:
the clinical efficacy of prolotherapy.
Brandt, D. and Lohmander, L. (eds), Osteoarthritis.
Oxford: Oxford University Press, pp: 9–16.

Conclusion Gupta, S., Hawker, G., Laporte, A., Croxford, R. and

Prolotherapy with three intra-articular injections of Coyte, P. (2005) The economic burden of disabling
hypertonic dextrose given 4 weeks apart for selected hip and knee osteoarthritis (OA) from the perspective
of individuals living with this condition. Rheumatology
patients with moderate knee OA resulted in statisti-
44: 1531–1537.
cally significant improvements in validated pain,
ROM, as well as in WOMAC-based function scores Hauser, R. and Hauser, M. (eds) (2007) Prolo Your
when baseline levels were compared at 24 weeks. Pain Away, Curing Chronic Pain with Prolotherapy.
Further studies with randomized controlled trials Updated third edition. Chicago, IL: Beulah Land
involving a comparison group are suggested to con- Press.
firm the obtained findings. Hashemi, S., Madadi, F., Razavi, S., Nikooseresht,
M., Kiyabi, F. and Nasiripour, S. (2010) Intra-
Acknowledgements articular hyaluronic acid injections versus dextrose
We greatly acknowledge Dr Morteza Ghojazadeh prolotherapy in the treatment of osteoarthritic knee
for his kind help in providing statistical analysis pain. TU M J 70: 119–125.
consultation. The authors are also indebted to the Hochberg, M., Altman, R., April, K., Benkhalti,
Physical Medicine and Rehabilitation Research M., Guyatt, G., McGowan, J. et al. (2012)
Center, Tabriz University of Medical Sciences, American College of Rheumatology 2012
Iran for its support. recommendations for the use of nonpharmacologic
and pharmacologic therapies in osteoarthritis
Funding of the hand, hip, and knee. Arthritis Care Res
This research received no specific grant from any (Hoboken) 64: 465–474.
funding agency in the public, commercial, or not- Hochberg, M., Perlmutter, D., Hudson, J. and
for-profit sectors. Altman, R. (1996) Preferences in the management of
osteoarthritis of the hip and knee: results of a survey
Conflict of interest statement of community-based rheumatologists in the United
The authors declare that there is no conflict of States. Arthritis Care Res 9: 170–176.
interest. Jensen, K., Rabago, D., Best, T., Patterson, J. and
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