Autologous Growth Factor Injections in Chronic Tendinopathy SR
Autologous Growth Factor Injections in Chronic Tendinopathy SR
British Medical Bulletin 2010; 95: 63–77 & The Author 2010. Published by Oxford University Press. All rights reserved.
DOI:10.1093/bmb/ldq006 For permissions, please e-mail: [email protected]
R. J. de Vos et al.
Introduction
Chronic painful tendon disorders are common in athletic and sedentary
individuals.1 – 4 They are more common in middle age, and with
increasing in sports participation at increasing ages, they are becoming
more frequent.1,2 The Achilles tendon, patella tendon, wrist extensors,
plantar fascia and supraspinatus tendon are commonly affected larger
tendons.5 Multiple aetiological factors probably play a role in the
pathogenesis of these conditions.1 – 5
Methods
Literature search
A comprehensive, systematic literature search was performed in
October 2009. The databases of PubMed, MEDLINE, EMBASE,
CINAHL and the Cochrane library were searched without time limits.
The following key words were used in differing combinations: ‘tendino-
pathy’, ‘tendinosis’, ‘tendinitis’, ‘tendons’, ‘tennis elbow’, ‘plantar fas-
ciitis’, ‘platelet rich plasma’, ‘platelet transfusion’, ‘autologous blood’
or ‘injection’. The search was limited to articles in English, and only
human studies were included. All titles and abstracts were assessed by
two researchers, and all relevant articles were obtained. All bibliogra-
Study selection
Articles were suitable (inclusion criteria) if the subjects had been clini-
cally diagnosed as having chronic tendinopathy. The design had to be a
prospective clinical study; randomized controlled trial (RCT), non-
randomized clinical trial (CCT) or prospective case series. There had to
be a well-described intervention in the form of an injection with either
PRP or autologous blood. The outcome had to be reported in terms of
pain and/or function.
Data extraction
Two researchers independently recorded the study design, population,
intervention, outcome measure and outcome using standardized data
extraction forms.13 To assess the efficacy of the interventions, mean
values of the continuous outcomes were extracted from the published
articles.
Quality assessment
The studies included were scored using the PEDro (Physiotherapy
Evidence Database) score.14 The PEDro score is an 11-point list using
yes and no answers. The first statement pertains to the external validity
Items
of the study and is not used to compute the final quality score. The
score (0– 10) is the number of positive answers on questions 2– 11. The
PEDro items are shown in Table 1.
To assess the reliability of consensus ratings using the PEDro scale, a
study was conducted by Maher et al.14 A random selection of 120
RCTs was assessed four times by four different raters. Intraclass corre-
lation coefficient for consensus ratings using the PEDro scale showed
to be 0.68, which compares to a ‘fair’ to ‘good’ reliability.15 It was
suggested that the PEDro scale has sufficient reliability for its use in
systematic reviews of physiotherapy trials,14 and recently it has been
used in a systematic review on the effects of exercise treatment in
tendinopathy.16
A PEDro score of 6 or higher is considered to represent a high-quality
study.16 The results of the quality assessments of the individual trials
were used to classify the level of evidence.17 This qualitative analysis
was performed with five levels of evidence based upon the quality and
results of clinical studies:
Studies with a high methodological score using the PEDro scale were
considered as high-quality studies and those with a low PEDro score
were considered low-quality studies.
Results
Literature search
Thirteen studies were included after screening. Two studies were
excluded (figure 1).43,44 Eleven studies were suitable for quality assess-
ment and were assessed using the PEDro score.
Participants
The mean number of subjects was 40.5 (SD 24.6) with a range 20–
100. Four studies were on patients with chronic tendinopathy of the
wrist extensors (tennis elbow)18,19,23,25 of which one study on both
wrist extensor and flexor tendinopathy (golfer’s elbow).25 One study
evaluated the treatment effect on tendinopathy of wrist flexors.20
Patients with chronic plantar fasciopathy were treated in three
studies24,27,28 and three studies had examined patients with chronic
patellar tendinopathy.21,22,26
Interventions
There were eight studies on the effects of autologous blood injec-
tions,18 – 21,23,24,27,28 of which five studies used this in combination
with a local anaesthetic18 – 21,24 and the other three studies applied only
autologous blood.23,27,28
There were three studies on PRP injections,22,25,26 of which one used
an additional local anaesthetic25 and two did not report whether local
anaesthesia was used.22,26 In three studies a single injection,24,25,27 in
one study two injections21 and in two studies three injections22,26 were
used. In the other five studies, a varying number of injections (1 –3)
were given.18 – 20,23,28 The PRP was prepared using a single25 or
double22,26 centrifuging process. In two studies, calcium was added to
the PRP for activation of the platelets.22,26
Outcome measures
Ten of the 11 studies used a visual analogue scale or ordinal scale to
measure pain.18 – 20,22 – 28 In four studies, the elbow function was quan-
tified using the Nirschl score.18 – 20,23 The Nirschl score runs from 1;
Reference Number of Study Inclusion Intervention Control group(s) Primary outcome Follow-up Outcome in Outcome in control
participants design criteria measures (months) intervention group(s) (%
group (% improvement)
improvement)
Edwards and 28 Case series Wrist extensor 1 –3 autologous — Pain scale (0 –10) 9.5 Mean pain score: —
Calandruccio18 tendinopathy blood 7.8 to 2.3 (71%)
injection(s)
Nirschl score (0 –7) Mean Nirschl
score: 6.5 to 2.0
(69%)
Mishra and 20 CCT Wrist extensor 1 PRP injection C: 1 anaesthetic VAS score (0 –100) 25.6 Mean VAS score: C: Mean VAS score:
Pavelko25 and flexor injection 80.3 to 5.7 NA
tendinopathy (93%)
Modified Mayo Mean Modified Mean Modified
elbow score (0 – 100) Mayo elbow Mayo elbow score:
score: NA NA
Suresh et al.20 20 Case series Wrist flexor 2 –3 autologous — VAS score (0 –10) 10 Mean VAS score: —
tendinopathy blood injections 8.0 to 2.2 (73%)
Nirschl score (0 –7) Median Nirschl
score: 6.0 to 1.0
(83%)
Connell et al.19 35 Case series Wrist extensor 2 –3 autologous — VAS score (0 –10) 6 Median VAS —
tendinopathy blood injections score: 9.0 to 0.0
Continued
R. J. de Vos et al.
Table 2 Continued
Reference Number of Study Inclusion Intervention Control group(s) Primary outcome Follow-up Outcome in Outcome in control
participants design criteria measures (months) intervention group(s) (%
group (% improvement)
improvement)
Improvements were calculated after correcting for scale and baseline score. CCT, non-randomized clinical trial; RCT, randomized controlled trial; VAS, visual analogue scale;
VISA-P, Victorian Institute of Sports Assessment-Patella; AOFAS, American Orthopaedics Foot and Ankle (rearfoot score); NA, not available; C, control group. *Significant
improvement in favour of autologous growth factor injection. †No significant difference with control group. ‡Significant improvement in favour of control group.
Outcomes
All the intervention groups reported a significant improvement in the
pain and/or function scores with the mean improvement being 66%
(SD 19, range 33– 100). The outcomes in the control groups also
improved significantly in all the studies with a mean improvement of
57% (SD 18, range 32 –87). These improvements were reported after a
mean follow-up of 9.4 months (SD 6.0). There was in none of the
included studies a beneficial effect on pain score at final follow-up
after autologous growth factor injections when compared with a
control group.24,26 – 28 One study reported a significant improvement
on the functional Tegner score when compared with the control group,
but the statistical baseline difference in Tegner score between these
groups was not reported.26 In four other control groups, there were
similar results on pain and/or function when compared with autolo-
gous growth factor injections.24,27,28 In two control groups, there was
a significant improvement on pain in favour of the control group.27
Table 2 gives an overview of these differences.
Sample-size calculation
Only one trial reported a sample-size calculation.22 Kon et al. reported
that 20 cases were needed to detect a clinically important increase of
Table 3 Particular scoring of the included studies for methodological quality according to
the PEDro score.
1 2 3 4 5 6 7 8 9 10 11
18
Edwards and Calandruccio þ 2 2 2 2 2 2 þ þ 2 2 2/10
Mishra and Pavelko25 þ 2 2 2 2 2 2 2 2 þ þ 2/10
Suresh et al.20 þ 2 2 2 2 2 2 2 2 2 þ 1/10
Connell et al.19 þ 2 2 2 2 2 2 2 2 2 þ 1/10
Kiter et al.28 þ þ 2 þ 2 2 þ þ þ þ þ 7/10
Ul Gani et al.23 þ 2 2 2 2 2 2 þ þ 2 2 2/10
James et al.21 þ 2 2 2 2 2 2 þ 2 2 þ 2/10
Lee and Ahmad24 þ þ 2 þ 2 2 þ þ þ þ þ 7/10
Kon et al.22 þ 2 2 2 2 2 2 þ þ 2 þ 3/10
Filardo et al.26 þ 2 2 2 2 2 2 þ þ þ þ 4/10
The total score was defined by the number of positive answers on questions 2–11 (0 –10).
15 points on the VAS score. All other included studies did not report
using a sample-size calculation.
Methodological quality
The PEDro scores for the 11 studies are shown in Table 3. The scores
ranged from 1 to 7 with an average of 3.4 (SD 2.3). Three studies were
considered as being high quality (PEDro score 6) and the other eight
studies were of low quality (PEDro score , 6). All the studies reported
the inclusion criteria. A comparison to another treatment was per-
formed in five studies, and randomization was used in two studies.
Blinding of the treatment was undertaken for patients in one study,27
for the treating physician in none of the studies and for the outcome
assessor in three studies.24,27,28 In three studies, more than 15% of the
patients were lost to follow-up,19,20,25 and in four studies, the data
analysis was not performed on an ‘intention to treat’ basis.19 – 21,25
Two studies had poor reporting of the statistical analysis.18,23
Level of evidence
Until now, three high-quality studies24,27,28 on the use of autologous
growth factor injections (all used autologous blood injections) for the
management of chronic tendinopathy showed no significant improve-
ment when compared with a control group. One study showed a sig-
nificantly superior improvement after a corticosteroid injection in
comparison with one single autologous blood injection.27 Two of these
Discussion
A total of 11 articles were suitable for inclusion in this systematic
review on the use of autologous growth factors in the treatment of
Conclusion
There is strong evidence that autologous blood injections do not
improve pain and/or function compared with other treatment options.
There is only limited evidence that PRP injections are beneficial. All
three high-quality studies on the use of autologous growth factor injec-
tions in the management of chronic tendinopathy showed no benefit.
All studies did show an effect on pain and function in time, but many
are seriously methodologically flawed. To date, there is strong evidence
that the use of injections with autologous blood should not be rec-
ommended, and there is limited evidence to support the use of injec-
tions with PRP in the treatment of chronic tendinopathy. Further
studies using a proper control group, randomization, blinding and vali-
dated disease-specific outcome measures for pain and function are
needed.
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