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To evaluate the effect of combining photo-activation therapy with platelet-rich plasma injections for the novel treatment of osteoarthritis

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Abstract

Objective To evaluate the effect of combining photo-activation therapy with platelet-rich plasma injections for the novel treatment of osteoarthritis. Design We present a case report of osteoarthritis of the knee treated with photo-activated platelet-rich plasma injections (PAPRP). Methods After utilising conventional osteoarthritis treatment methods a patient underwent a course of PAPRP injections. The patient outcome was measured using the numerical pain rating scale (NPRS) and the Western Ontario and McMaster Universities Arthritis (WOMAC) Index. Results Following treatment the patient reported improvements in both pain and function as measured by the NPRS and WOMAC Index, respectively. The patient was followed up for 18 weeks, at which time no significant complications were noted. Conclusions In this case report of osteoarthritis, with strict control of conventional therapy variables, PAPRP injections demonstrated improvement in all recorded outcome measures. The results of this case report highlight the need to further investigate the use of PAPRP in the treatment of symptomatic knee osteoarthritis.
CASE REPORT
To evaluate the effect of combining photo-activation
therapy with platelet-rich plasma injections for the
novel treatment of osteoarthritis
Julien Ben Freitag,
1
Adele Barnard
2
1
Prahran Sports Medicine
Centre, Lifecare, Prahran,
Victoria, Australia
2
MetroSpinal Clinic, Cauleld
South, Melbourne, Victoria,
Australia
Correspondence to
Dr Julien Ben Freitag,
julien.freitag@me.com
To cite: Freitag JB,
Barnard A. BMJ Case Rep
Published online: [please
include Day Month Year]
doi:10.1136/bcr-2012-
007463
SUMMARY
Objective To evaluate the effect of combining photo-
activation therapy with platelet-rich plasma injections for
the novel treatment of osteoarthritis.
Design We present a case report of osteoarthritis of
the knee treated with photo-activated platelet-rich
plasma injections (PAPRP).
Methods After utilising conventional osteoarthritis
treatment methods a patient underwent a course of
PAPRP injections. The patient outcome was measured
using the numerical pain rating scale (NPRS) and the
Western Ontario and McMaster Universities Arthritis
(WOMAC) Index.
Results Following treatment the patient reported
improvements in both pain and function as measured by
the NPRS and WOMAC Index, respectively. The patient
was followed up for 18 weeks, at which time no
signicant complications were noted.
Conclusions In this case report of osteoarthritis, with
strict control of conventional therapy variables, PAPRP
injections demonstrated improvement in all recorded
outcome measures. The results of this case report
highlight the need to further investigate the use of
PAPRP in the treatment of symptomatic knee
osteoarthritis.
BACKGROUND
Arthritis is a major cause of disability and chronic
pain and has a signicant economical impact.
13
Osteoarthritis (OA) is a progressive and degenera-
tive form of arthritis that does not discriminate
against age. Osteoarthritis is difcult to treat, with
most current medical treatment strategies aimed at
pain reduction and/or symptom control rather
than biochemical disease modication. Available
pharmacological treatments are limited and often
bear unwanted side effects.
4
Viscosupplement/hyaluronic acid (HA) intra-
articular injections have been used for many years as
an adjunctive treatment in conservative management
of osteoarthritis. However, the mechanism of action
of HA is uncertain,
5
with some studies suggesting
little improvement beyond that achieved with
placebo injections.
6
Recent research has focused on the catabolic
cytokines involved in destruction of hyaline cartil-
age and joint degeneration. Interleukin-1 (IL-1) has
been identied as a potent mediator of cartilage
loss
79
and reciprocally IL-1 receptor antagonist
(IL-1RA) has been shown to limit the intra-articular
actions of IL-1.
1012
Autologous conditioned serum
(ACS) is an injectable IL-1RA medium that has
been used in Europe for the treatment of osteoarth-
ritis.
12
Research has indicated signicant improve-
ment in symptoms of OA post ACS therapy,
12
however, further research is required to determine
whether ACS is actually disease modifying. Use of
ACS is limited due to cost and logistical hurdles
such as incubating the autolgous blood overnight
prior to reinjection.
Owing to the limitations of ACS, the research
focus has shifted towards platelet-rich plasma
(PRP) injections, where reports have demonstrated
improved cartilage matrix expression in animal and
in-vitro studies, along with the synthesis of hylauro-
nic acid.
1317
Platelets, once originally thought to
act solely in haemostasis at sites of vascular injury,
are now known to contain an abundance of growth
factors and cytokines, crucial to soft-tissue healing.
In fact, a retrospective cohort study has indicated
signicant reduction in pain postintrarticular injec-
tion of PRP compared with hyaluroinc acid supple-
ments.
16
Similarly, a recent study of patients with
grades IIII OA, demonstrated signicantly
improved pain and function following PRP, when
compared with the hyaluronic acid injection
control group.
18
Beside PRP, photo-activation therapy has been
shown to increase expression of leucocyte-derived
anti-inammatory cytokines (IL-1RA) and also to
cause reduction in proinammatory cytokines (IL-2
and 6).
19 20
Thus, a combined photo-activated PRP
(PAPRP) preparation may offer a novel method for
treatment of osteoarthritis that combines the
proven benets of ACS with potentially disease-
modifying properties of PRP.
CASE PRESENTATION
A 50-year-old woman presented to a Sports and
Exercise Medicine Clinic with progressive and
symptomatic left knee osteoarthritis. Radiological
examination using x-ray (Kellgren and Lawrence
Protocol
21
) conrmed tricompartmental osteoarth-
ritis with grade IV medial compartment chondro-
malacia and grades IIIII changes of both her
lateral and patellofemoral compartments.
The pre-existing conservative management pro-
gramme included podiatric biomechanical assess-
ment and orthotic alteration, daily weight bearing,
moderate-intensity exercise and signicant weight
loss in the preceding 12 months (>30 kg). In add-
ition, glucosamine sulfate (1500 mg daily) along
with other daily supplements were being taken.
Freitag JB, et al.BMJ Case Rep 2013. doi:10.1136/bcr-2012-007463 1
Novel treatment (new drug/intervention; established drug/procedure in new situation)
Non-steroidal anti-inammatory drugs (NSAIDs) were not pre-
scribed due to a strong paternal family history of ischaemic
heart disease at an early age. Strict regular long-acting paraceta-
mol (1330 mg twice daily) was prescribed at her initial
consultation.
The patient sought advice on possible additional treatments
for her knee arthritis and made specic enquiries regarding PRP
intra-articular injections. As such, written information and edu-
cation was provided regarding PRP and its use within osteoarth-
ritis, including relevant alternatives and possible risks involved.
Given that the patient had radiological proven osteoarthritis,
failed conservative treatments and was otherwise well, she was
assessed as a suitable candidate for the trial of intra-articular
PRP. Formal written informed consent was obtained prior to
commencement of treatment.
INVESTIGATIONS
Radiological examination using x-ray conrmed tricompartmen-
tal osteoarthritis with grade IV medial compartment chondro-
malacia and grades IIIII changes of both her lateral and
patellofemoral compartments.
TREATMENT
Photo-activated PRP preparation
Autologous blood (24 mls) was taken from the study participant
and separated into 3×8.5 ml BD Vacutainers (BD, Franklin
Lakes, New Jersey, USA) containing ACD (trisodium citrate
22 g/l, citric acid 8 g/l and dextrose 24.5 g/l) to prevent clotting.
The tubes were centrifuged at 1000 rpm for 10 min to create a
platelet-poor plasma (PPP) level, a middle buffy coat level (high
in platelets and leucocytes) and a red blood cell layer.
PPP was withdrawn from each tube to the level of 10 mm
above the buffy coat and discarded. The remaining plasma,
along with the buffy coat and 2 mm of the red cell layer were
withdrawn into a single sterile tube and exposed to photo-
activation for 10 min. Photo-activation was achieved using the
commercial Adi-Light 2 device (AdiStem Ltd, Hong Kong).
Injection method
Under strict sterile conditions and ultrasound guidance, a sterile
21-gauge needle was inserted using a medial approach to the
medial knee compartment. Four millilitres of PAPRP was
injected with no concurrent use of local anaesthetic. Overall,
the patient received three PAPRP injections, each 1 week apart
(weeks 0, 1 and 2).
Potential adverse effects
Previous studies using PRP therapy have indicated minimal
adverse effects.
18 22
Spakova et al documented a short self-
limited aggrevation of osteoarthritis symptoms in some patients.
As this is an intra-articular injection the most signicant risk is
that of infection.
Analysis method and outcome measures
Prospective analysis of patient outcomes to intra-articular
PAPRP injection included the Numerical Pain Rating Scale
(NPRS)
23
and Western Ontario and McMaster Universities
Arthritis Index (WOMAC Index 3.0).
24 25
The WOMAC Knee
Score is a validated disease-specic functional quality-of-life
instrument developed to assess pain, stiffness and physical func-
tion in patients with knee osteoarthritis.
24 25
NPRS was recorded prior to and 2 weeks following com-
mencement of paracetamol, and prior to each injection, with
follow-up intervals occurring at weeks 3, 6, 10, 14 and 18. The
WOMAC Knee Score was recorded prior to the rst injection
and at weeks 6, 10, 14 and 18. In addition to the above treat-
ment outcome measures, patient satisfaction with treatment was
further assessed at week 18 by recording a percentage perceived
improvement.
OUTCOME AND FOLLOW-UP
Results
Following 2-weeks commencement of regular paracetamol and
prior to undergoing PAPRP therapy, the patient reduced their
pain from 5 to 4 on the NPRS. NPRS improved further after
the rst injection of PAPRP and reduced to 0 by week 6. NPRS
remained between 0 and 1 from week 4 to nal data collection
in week 18 (gure 1).
WOMAC Knee Score at baseline indicated signicant pain,
physical and functional impairment (Global WOMAC Score
59.38). At week 6, the Global WOMAC Score had improved by
65% and remained so up to the nal data collection at week 18
(gure 2).
At 18 weeks following the initial PAPRP injection, a percent-
age perceived improvement of 80% was reported by the patient.
A small are upof knee discomfort following the second
PAPRP injection, lasting 2 days, was reported by the patient.
This was not associated with a knee effusion and no increase in
analgesia was required. No other complications were noted.
DISCUSSION
This report highlights the novel treatment of osteoarthritis by
combining the anti-inammatory characteristics of photo-
activation with the disease-modifying properties of PRP.
Post-PAPRP therapy, the patient demonstrated improvement in
all the recorded treatment outcome measures. NPRS improved at
week 1 (7 days post rst injection), suggesting an immediate anti-
inammatory and analgesic benet of PAPRP. Sustained improve-
ments in NPRS were observed for 18 weeks post-therapy.
Concurrent results were observed in the pain subset of the
WOMAC index. Both stiffness and function were also improved
on the WOMAC when measured at 6 weeks post-PAPRP.
A small are upof discomfort was observed following the
second PAPRP injection; however, this was short-lived and did
not occur with the rst or third injection. Similar short-term pain
increases have been observed in the literature following injection,
which also resulted in no long-term complications.
18 22
At present PRP literature is limited; however, the small but
growing body of evidence promotes the use of PRP therapy in
OA. In two separate studies, PRP therapy (without photo-
activation) has demonstrated improved pain and function when
Figure 1 Numerical pain rating scale. Pain reduced following
photo-activated platelet-rich plasma injections for the treatment of
osteoarthritis in the knee.
2 Freitag JB, et al.BMJ Case Rep 2013. doi:10.1136/bcr-2012-007463
Novel treatment (new drug/intervention; established drug/procedure in new situation)
compared to hyaluronic acid injections for OA.
16 18
This limited
single case report does not aim at providing conclusive evidence
for the combined use of PAPRP, rather it aims to promote further
discussion and thought into optimising current PRP protocols
and developing controlled-randomised studies to further investi-
gate the role of photo-activation in PRP preparation.
Our preliminary ndings suggest that PAPRP may have
promise in the treatment of symptomatic knee OA. In a single
case report with strict control of other treatment variables and
prior maximisation of conservative OA treatment, PAPRP
therapy was associated with improvement in all the recorded
treatment outcome measures. Symptomatic improvement was
achieved within 1 week of the rst injection.
The novel method of combining photo-activation of PRP for
the treatment of symptomatic arthritis has not previously been
described within the scientic literature. Previous publications
have shown the potential of PRP in the treatment of osteoarth-
ritis but unlike this single case report have not recorded short-
term treatment outcome data (within 1 month).
1618
This case
study indicates the potential for photo-activated PRP to have
both short-term and extended benets in improving symptom-
atic arthritis.
While recognising the low level of evidence, the results of this
limited case report highlight the need to further investigate
through a more structured and appropriately powered
randomised-controlled trialthe combined use of photo-
activation and PRP and so to determine both the clinical efcacy
and mechanistic properties of PAPRP.
Depending on the results of further research, PAPRP may
have a role in the non-surgical management of knee osteoarth-
ritis. This is a promising development for the patient population
who remain symptomatic despite maximal conservative manage-
ment and who are unsuitable for surgical intervention.
Learning points
Current pharmacological treatments for osteoarthritis are
limited.
Photo-activated platelet-rich plasma (PRP) shows promise in
the treatment of symptomatic knee osteoarthritis.
Photo-activation therapy of PRP may improve its
anti-inammatory properties and result in earlier
symptomatic improvement.
Further research is required to determine if photo-activated
PRP has structural disease-modifying properties.
Competing interests None.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
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Pain, stiffness and function improved
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plasma injections for the treatment of
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4 Freitag JB, et al.BMJ Case Rep 2013. doi:10.1136/bcr-2012-007463
Novel treatment (new drug/intervention; established drug/procedure in new situation)
... extremity function in patients with knee OA [20]. Freitag and Barnard showed improvement in pain (Numerical Pain Scale Rating) and WOMAC index scores in a case study using photoactivated PRP [21]. This case study shows similar results based on the outcome scores. ...
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This study aimed to find a simple, cost-effective, and time-efficient method for the preparation of platelet-rich plasma (PRP), so the acquired benefits will be readily available for multiple procedures in smaller outpatient clinics and to explore the safety and efficacy of the application of PRP in the treatment of degenerative lesions of articular cartilage of the knee. The study was designed as a prospective, cohort study with a control group. A total of 120 patients with Grade 1, 2, or 3 osteoarthritis according to the Kellgren and Lawrence grading scale were enrolled in the study. One group of patients was treated using three intra-articular applications of PRP, and the second group of patients was given three injections of hyaluronic acid. Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index and the 11-point pain intensity Numeric Rating Scale. On average, a 4.5-fold increase in platelet concentration was obtained in the PRP group. No severe adverse events were observed. Statistically significantly better results in the Western Ontario and McMaster Universities Osteoarthritis Index and Numeric Rating Scale scores were recorded in a group of patients who received PRP injections after a 3- and 6-mo follow-up. Our preliminary findings support the application of autologous PRP as an effective and safe method in the treatment of the initial stages of knee osteoarthritis. Further studies are needed to confirm these results and to investigate the persistence of the beneficial effects observed.
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OBJECTIVE: This study aimed to find a simple, cost-effective, and time-efficient method for the preparation of platelet-rich plasma (PRP), so the acquired benefits will be readily available for multiple procedures in smaller outpatient clinics and to explore the safety and efficacy of the application of PRP in the treatment of degenerative lesions of articular cartilage of the knee. DESIGN: The study was designed as a prospective, cohort study with a control group. A total of 120 patients with Grade 1, 2, or 3 osteoarthritis according to the Kellgren and Lawrence grading scale were enrolled in the study. One group of patients was treated using three intra-articular applications of PRP, and the second group of patients was given three injections of hyaluronic acid. Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index and the 11-point pain intensity Numeric Rating Scale. RESULTS: On average, a 4.5-fold increase in platelet concentration was obtained in the PRP group. No severe adverse events were observed. Statistically significantly better results in the Western Ontario and McMaster Universities Osteoarthritis Index and Numeric Rating Scale scores were recorded in a group of patients who received PRP injections after a 3- and 6-mo follow-up. CONCLUSIONS: Our preliminary findings support the application of autologous PRP as an effective and safe method in the treatment of the initial stages of knee osteoarthritis. Further studies are needed to confirm these results and to investigate the persistence of the beneficial effects observed.
Article
To assess degree of cyclooxygenase-2 (COX-2) selectivity of a non-steroidal anti-inflammatory drug (NSAID) and risk of myocardial infarction (MI) or cerebrovascular accident (CVA). Prescription fill data were linked to medical records of a merged VA-Medicare dataset. NSAIDs were categorized by Cox-2 selectivity. Incidence of CVA and MI within 180 days of index prescription was assessed using Cox-proportional hazards models adjusted for gender, race, cardiovascular and pharmacological risk factors and propensity for prescription of highly COX-2 selective NSAIDs. Of 384,322 patients (97.5% men and 85.4% white), 79.4% were prescribed a poorly selective, 16.4% a moderately selective and 4.2% a highly selective NSAID. There were 985 incident cases of MI and 586 cases of CVA in >145 870 person-years. Highly selective agents had the highest rate of MI (12.3 per 1000 person-years; [95% CI: 12.2-12.3]) and CVA (8.1 per 1000 person-years; [95% CI: 8.0-8.2]). Periods without NSAID exposure were associated with lowest risk. In adjusted models, highly selective COX-2 selective NSAIDs were associated with a 61% increase in CVA and a 47% increase in MI, when compared with poorly selective NSAIDs. The risk of MI and CVA increases with any NSAID. Highly COX-2 selective NSAIDs confer the greatest risk.
Article
To evaluate the clinical effects of intraarticular platelet-rich plasma (PRP) injections in a small group of patients with primary and secondary osteoarthritis. Most of the current treatments for osteoarthritis are palliative and attack the symptoms rather than influencing the biochemical environment of the joint. Autologous platelet-rich plasma has emerged as a treatment option for tendinopathies and chronic wounds. In addition to release of growth factors, platelet-rich plasma also promotes concentrated anti-inflammatory signals including interleukin-1ra, which has been a focus of emerging treatments for osteoarthritis. In this single-center, uncontrolled, prospective preliminary study, 14 patients with primary and secondary knee osteoarthritis who met the study criteria received three platelet-rich plasma injections in the affected knee at ∼4-wk intervals. Outcome measures included the Brittberg-Peterson Visual Pain (Visual Analog Scale [VAS]), Activities, and Expectations score and the Knee Injury and Osteoarthritis Outcome Scores at preinjection visit at 2-, 5-, 11-, 18-, and 52-wk follow-up visits. Musculoskeletal ultrasound was used to measure cartilage thickness. There were no adverse events reported. The study demonstrated significant and almost linear improvements in Knee Injury and Osteoarthritis Outcome Scores, including pain and symptom relief. Brittberg-Peterson VAS showed many improvements including reduced pain after knee movement and at rest. Cartilage assessment was limited because of the small sample size. The majority of the patients expressed a favorable outcome at 12 mos after treatment. The positive trends and safety profile demonstrated could potentially be used to inspire a larger, blinded, and randomized clinical trial to determine whether platelet-rich plasma is safe and effective for the treatment of knee osteoarthritis.
Article
To investigate the therapeutic potential of administration of gelatin hydrogel microspheres containing platelet-rich plasma (PRP), by examining its effects on progression of osteoarthritis (OA) in a rabbit model. PRP and platelet-poor plasma (PPP) were prepared from rabbit blood. Adult rabbit chondrocytes were cultured in the alginate beads with the presence of 3% PRP or 3% PPP. Glycosaminoglycan (GAG) synthesis was quantified using dimethylmethylene blue assay. To confirm the anabolic effect of PRP in vivo, cartilage matrix gene expression was examined after intraarticular administration of PRP contained in gelatin hydrogel microspheres. The PRP contained in gelatin hydrogel microspheres was administered into the rabbit knee joint twice with an interval of 3 weeks, beginning 4 weeks after anterior cruciate ligament transection (ACLT). Ten weeks after ACLT, gross morphological and histological examinations were performed. PRP significantly stimulated chondrocyte GAG synthesis in vitro. In the knee joint, expression of proteoglycan core protein mRNA in the articular cartilage increased after administration of PRP contained in microspheres. Intraarticular injections of PRP in gelatin hydrogel microspheres significantly suppressed progression of OA in the ACLT rabbit model morphologically and histologically. The present findings indicate that sustained release of growth factors contained in PRP has preventive effects against OA progression. These preventive effects appear to be due to stimulation of cartilage matrix metabolism, caused by the growth factors contained in PRP.