Comparison Between Hyaluronic Acid and Platelet-Rich Plasma, Intra-articular Infiltration in the Treatment of Gonarthrosis Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Platelet-rich plasma intra-articular injections for cartilage degeneration and osteoarthritis: single- versus double-spinning approach Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions Treatment of Knee Joint Osteoarthritis with Autologous Platelet-Rich Plasma in Comparison with Hyaluronic Acid Intraarticular application of autologous conditioned serum (ACS) reduces bone tunnel widening after ACL reconstructive surgery in a randomized controlled trial Platelet-rich plasma (PRP) injections as an effective treatment for early osteoarthritis Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: a retrospective cohort study. A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. Injection of Platelet-Rich Plasma in Patients with Primary and Secondary Knee Osteoarthritis: A Pilot Study Comparison of intra-articular injections of plasma rich in growth factors (PRGF-Endoret) versus Durolane hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: a randomized controlled trial. Platelet-rich plasma injection is more effective than hyaluronic acid in the treatment of knee osteoarthritis. Treatment With Platelet-Rich Plasma Is More Effective Than Placebo for Knee Osteoarthritis
Background : Arthrosis is particularly prevalent in the knee . Infiltration treatment for gonarthrosis is among the most widely used techniques in orthopaedic practice . Purpose : To compare the clinical response of hyaluronic acid ( HA ) and platelet-rich plasma ( PRP ) treatment in 2 groups of patients affected by gonarthrosis . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 120 patients affected by clinical ly and radiographically documented gonarthrosis were included in this study . The gonarthrosis was grade d using the Kellgren-Lawrence radiographic classification scale . The 120 patients were r and omized into 2 study groups in a 1:1 ratio : 60 patients received 4 intra-articular injections of PRP ( specifically , autologous conditioned plasma [ ACP ] , 5.5 mL ) , and 60 patients received 4 intra-articular injections of HA ( 20 mg/2 mL ) . An unblinded physician performed infiltration once a week for 4 weeks into the knee affected by clinical ly relevant gonarthrosis ( in both groups ) . All patients were evaluated with the Western Ontario and McMaster ( WOMAC ) score before the infiltration and at 4 , 12 , and 24 weeks after the first injection . Results : Treatment with a local injection of ACP had a significant effect shortly after the final infiltration and a continuously improving sustained effect up to 24 weeks ( WOMAC score , 65.1 and 36.5 in the HA and ACP groups , respectively ; P < .001 ) , where the clinical outcomes were better compared with the results with HA . In the HA group , the worst results were obtained for grade III gonarthrosis , whereas the clinical results obtained in the ACP group did not show any statistically significant difference in terms of the grade of gonarthrosis . The mean WOMAC scores for grade III gonarthrosis were 74.85 in the HA group and 41.20 in the ACP group ( P < .001 ) . Conclusion : Treatment with ACP showed a significantly better clinical outcome than did treatment with HA , with sustained lower WOMAC scores . Treatment with HA did not seem to be effective in the patients with grade III gonarthrosis PURPOSE The aim of our study is to compare the efficacy of platelet-rich plasma ( PRP ) and viscosupplementation ( hyaluronic acid [ HA ] ) intra-articular injections for the treatment of knee cartilage degenerative lesions and osteoarthritis ( OA ) . METHODS The study involved 150 patients affected by cartilage degenerative lesions and early and severe OA . Fifty symptomatic patients were treated with 3 autologous PRP intra-articular injections and were evaluated prospect ively at enrollment and at 2- and 6-month follow-up . The results obtained were compared with 2 homogeneous groups of patients treated with HA injections . One group was treated with injections of high-molecular weight HA ; the other group was treated with low-molecular weight ( LW ) HA .  International Knee Documentation Committee and EQ VAS scores were used for clinical evaluation ; adverse events and patient satisfaction were also recorded . RESULTS At 2 months ' follow-up , the PRP and LW HA groups showed a similar improvement , with higher results compared with the high-molecular weight HA group ( P < .005 ) . At 6 months ' follow-up , better results were observed in the PRP group ( P < .005 ) . PRP and LW HA treatments offered similar results in patients aged over 50 years and in the treatment of advanced OA . PRP showed a better performance compared with HA in younger patients affected by cartilage lesions or early OA . CONCLUSIONS Autologous PRP injections showed more and longer efficacy than HA injections in reducing pain and symptoms and recovering articular function . Better results were achieved in younger and more active patients with a low degree of cartilage degeneration , whereas a worse outcome was obtained in more degenerated joints and in older patients , in whom results similar to those of viscosupplementation have been observed . LEVEL OF EVIDENCE Level II , prospect i ve comparative study Background Platelet Rich Plasma ( PRP ) , a blood-derived product rich in growth factors , is a promising treatment for cartilage defects but there is still a lack of clinical evidence . The aim of this study is to show , through a r and omized double blind prospect i ve trial , the efficacy of this procedure , by comparing PRP to Hyaluronic Acid ( HA ) injections for the treatment of knee chondropathy or osteoarthritis ( OA ) . Methods 109 patients ( 55 treated with HA and 54 with PRP )  were treated and evaluated at 12 months of follow-up . The patients were enrolled according to the following inclusion criteria : age > 18 years , history of chronic ( at least 4 months ) pain or swelling of the knee and imaging findings of degenerative changes of the joint ( Kellgren-Lawrence Score up to 3 ) . A cycle of 3 weekly injections was administered blindly . All patients were prospect ively evaluated before and at 2 , 6 , and 12 months after the treatment by : IKDC , EQ-VAS , TEGNER , and KOOS scores . Range of motion and knee circumference changes were measured over time . Adverse events and patient satisfaction were also recorded . Results Only minor adverse events were detected in some patients , such as mild pain and effusion after the injections , in particular in the PRP group , where a significantly higher post-injective pain reaction was observed ( p=0.039 ) . At the follow-up evaluations , both groups presented a clinical improvement but the comparison between the two groups showed a not statistically significant difference in all scores evaluated . A trend favorable for the PRP group was only found in patients with low grade articular degeneration ( Kellgren-Lawrence score up to 2 ) . Conclusions Results suggest that PRP injections offer a significant clinical improvement up to one year of follow-up . However , conversely to what was shown by the current literature , for middle-aged patients with moderate signs of OA , PRP results were not better than those obtained with HA injections , and thus it should not be considered as first line treatment . More promising results are shown for its use in low grade degeneration , but they still have to be confirmed Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Purpose To compare the safety and efficacy of two different approaches of platelet-rich plasma ( PRP ) production methods as intra-articular injection treatment for knee cartilage degenerative lesions and osteoarthritis ( OA ) . Methods The study involved 144 symptomatic patients affected by cartilage degenerative lesions and OA . Seventy-two patients were treated with 3  injections of platelet concentrate prepared with a single-spinning procedure ( PRGF ) , the other 72 with 3 injections of PRP obtained with a double-spinning approach . The patients were evaluated prospect ively at the enrollment and at 2 , 6 , and 12 months ’ follow-up with IKDC , EQ-VAS and Tegner scores ; adverse events and patient satisfaction were also recorded . Results Both treatment groups presented a statistically significant improvement in all the scores evaluated at all the follow-up times . Better results were achieved in both groups in younger patients with a lower degree of cartilage degeneration . The comparative analysis showed similar improvements with the two procedures : in particular , IKDC subjective evaluation increased from 45.0 ± 10.1 to 59.0 ± 16.2 , 61.3 ± 16.3 , and 61.6 ± 16.2 at 2 , 6 , and 12 months in the PRGF group , and from 42.1 ± 13.5 to 60.8 ± 16.6 , 62.5 ± 19.9 , and 59.9 ± 20.0 at 2 , 6 , and 12 months in the PRP group , respectively . Concerning adverse events , more swelling ( P = 0.03 ) and pain reaction ( P = 0.0005 ) , were found after PRP injections . Conclusions Although PRP injections produced more pain and swelling reaction with respect to that produced by PRGF , similar results were found at the follow-up times , with a significant clinical improvement with respect to the basal level . Better results were achieved in younger patients with a low degree of cartilage degeneration . Level of evidence II Platelet-rich plasma ( PRP ) is a natural concentrate of autologous blood growth factors experimented in different fields of medicine in order to test its potential to enhance tissue regeneration . The aim of our study is to explore this novel approach to treat degenerative lesions of articular cartilage of the knee . One hundred consecutive patients , affected by chronic degenerative condition of the knee , were treated with PRP intra-articular injections ( 115 knees treated ) . The procedure consisted of 150-ml of venous blood collected and twice centrifugated : 3 PRP units of 5 ml each were used for the injections . Patients were clinical ly prospect ively evaluated before and at the end of the treatment , and at 6 and 12 months follow-up . IKDC , objective and subjective , and EQ VAS were used for clinical evaluation . Statistical analysis was performed to evaluate the significance of sex , age , grade of OA and BMI . A statistically significant improvement of all clinical scores was obtained from the basal evaluation to the end of the therapy and at 6–12 months follow-up ( P < 0.0005 ) . The results remained stable from the end of the therapy to 6 months follow up , whereas they became significantly worse at 12 months follow up ( P = 0.02 ) , even if still significantly higher respect to the basal level ( P < 0.0005 ) . The preliminary results indicate that the treatment with PRP injections is safe and has the potential to reduce pain and improve knee function and quality of live in younger patients with low degree of articular degeneration Objective This study aim ed 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 design ed as a prospect i ve , 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 Purpose Pro-inflammatory cytokines play a pivotal role in osteoarthritis , as well as in bone tunnel widening after ACL reconstructive surgery . A new treatment option is to administer autologous conditioned serum ( ACS ) containing endogenous anti-inflammatory cytokines including IL-1Ra and growth factors ( IGF-1 , PDGF , and TGF-β1 , among others ) in the liquid blood phase . The purpose of this trial was to establish whether the postoperative outcome could be affected by intraarticular application of ACS . Methods In a prospect i ve , r and omized , double-blinded , placebo-controlled trial with two parallel groups , 62 patients were treated .  Bone tunnel width was measured by CT scans , while clinical efficacy was assessed by patient-administered outcome instruments ( WOMAC , IKDC 2000 ) up to 1 year following the ACL reconstruction in patients receiving either ACS ( Group A ) or placebo ( Group B ) . We compared the levels and dynamics of IL-1β concentrations in the synovial liquid and examined the correlation between the levels of IL-1β at three different postoperative points . Results Bone tunnel enlargement was significantly less ( 6 months : 8 % , 12 months : 13 % ) in Group A than in Group B ( 6 months : 31 % , 12 months : 38 % ) . Clinical outcomes ( WOMAC , IKDC 2000 ) were consistently better in patients treated with ACS at all data points and for all outcome parameters , and there were statistically significant differences in the WOMAC stiffness subscale after 1 year . The decrease in IL-1β synovial fluid concentration was more pronounced in the ACS group , and values were lower , to a statistically significant degree , in the ACS group at day 10 . Conclusion The intraarticular administration/injection of ACS results in decreased bone tunnel widening after ACL reconstructive surgery . Level of evidence Therapeutic study , R and omized controlled trial ( significant differences and narrow confidence intervals ) , Level The aims of this study were to analyze the range of cartilage damage and patellofemoral joint ( PFJ ) degeneration in degenerative osteoarthritis ( OA ) and determine the duration for the positive effects of platelet-rich plasma ( PRP ) injection . This study included 65 patients suffering from OA that were treated with intra-articular PRP injection .  The patients were prospect ively evaluated at 1 , 3 , 6 , 9 , and 12 months after the procedure using a visual analogue scale ( VAS ) score and an International Knee Documentation Committee ( IKDC ) score . Clinical improvement in the average VAS score from 7.4 before the procedure to 4.2 at 6 months post-procedure had been reported , but the symptoms tended to deteriorate to 5.0 1 year after injection . The IKDC score also showed statistical significance ( P < 0.05 ) . Patients reported relapsed pain 8.8 months after the procedure . Developing degeneration according to the Kellgren – Lawrence grade reduced the clinical effects of PRP ( P < 0.05 ) and also accelerated the time for feeling relapsed pain ( P < 0.05 ) . There was a statistically significant negative correlation between patient age and the PRP potential in the VAS score ( slope = 0.1667 ) and IKDC score ( slope = 1.3333 ) . The presence of PFJ degeneration is expected to produce a worse outcome ( P < 0.05 ) . While intra-articular PRP injection can be used for the treatment of early OA , increasing age , and developing degeneration result in a decreased potential for PRP injection therapy OBJECTIVE To obtain preliminary information about the effectiveness of intra-articular injections of an autologous preparation rich in growth factors ( PRGF ) for knee OA treatment to be explored further in future studies . METHODS We have characterized PRGF treatment by platelet count and concentration of relevant growth factors ( TGF-Beta1 , PDGF-AB , VEGF-A ; HGF and IGF-I ) involved in healing mechanisms . We have performed an observational retrospective cohort study using hyaluronan injections as a control . Each group included 30 patients with OA of the knee , matched according to age , sex , body mass index and radiographic severity . Both treatments were based on three weekly injections . Clinical outcome was examined using the WOMAC question naires prior to treatment and at 5 weeks after treatment . RESULTS The observed success rates by week 5 for the pain subscale reached 33.4 % for the PRGF group and 10 % for the hyaluronan group . The difference was attributed exclusively to the treatment modality , p = 0.004 . The percent reductions in the physical function subscale and overall WOMAC at 5 weeks were also associated solely with treatment modality in favour of PRGF , p = 0.043 and p = 0.010 respectively . CONCLUSIONS Although these preliminary results need to be evaluated in a r and omized clinical trial , they provide useful infomration about the safety of PRGF and open new perspectives on autologous treatments for joint diseases PURPOSE This multicenter , double-blind clinical trial evaluated and compared the efficacy and safety of PRGF-Endoret ( BTI Biotechnology Institute , Vitoria-Gasteiz , Spain ) , an autologous biological therapy for regenerative purpose s , versus hyaluronic acid ( HA ) as a short-term treatment for knee pain from osteoarthritis . METHODS We r and omly assigned 176 patients with symptomatic knee osteoarthritis to receive infiltrations with PRGF-Endoret or with HA ( 3 injections on a weekly basis ) . The primary outcome measure was a 50 % decrease in knee pain from baseline to week 24 . As secondary outcomes , we also assessed pain , stiffness , and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index ; the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International St and ing Committee for Clinical Trials Response Criteria Initiative ( OMERACT-OARSI ) ; and safety . RESULTS The mean age of the patients was 59.8 years , and 52 % were women . Compared with the rate of response to HA , the rate of response to PRGF-Endoret was 14.1 percentage points higher ( 95 % confidence interval , 0.5 to 27.6 ; P = .044 ) . Regarding the secondary outcome measures , the rate of response to PRGF-Endoret was higher in all cases , although no significant differences were reached . Adverse events were mild and evenly distributed between the groups . CONCLUSIONS Plasma rich in growth factors showed superior short-term results when compared with HA in a r and omized controlled trial , with a comparable safety profile , in alleviating symptoms of mild to moderate osteoarthritis of the knee . LEVEL OF EVIDENCE Level I , r and omized controlled multicenter trial Sampson S , Reed M , Silvers H , Meng M , M and elbaum B : Injection of platelet-rich plasma in patients with primary and secondary knee osteoarthritis : A pilot study . Objective : 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 . Design : In this single-center , uncontrolled , prospect i ve 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 . Results : 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 . Conclusions : The positive trends and safety profile demonstrated could potentially be used to inspire a larger , blinded , and r and omized clinical trial to determine whether platelet-rich plasma is safe and effective for the treatment of knee osteoarthritis PURPOSE The purpose of this study was to compare the efficacy and safety in a r and omized , clinical trial of 3 injections of PRGF-Endoret ( BTI Biotechnology Institute , Vitoria , Spain ) versus one single intra-articular injection of Durolane hyaluronic acid ( HA ) ( Q-MED AB , Uppsala , Sweden ) as a treatment for reducing symptoms in patients with knee osteoarthritis ( OA ) . METHODS Ninety-six patients with symptomatic knee OA were r and omly assigned to receive PRGF-Endoret ( 3 injections on a weekly basis ) or one infiltration with Durolane HA . The primary outcome measures were a 30 % decrease and a 50 % decrease in the summed score for the pain , physical function , and stiffness subscales of the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and Lequesne scores from baseline to weeks 24 and 48 . The percentage of OMERACT-OARSI ( Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International St and ing Committee for Clinical Trials Response Criteria Initiative ) responders was also documented . As secondary outcomes , pain , stiffness , and physical function by use of the WOMAC and the Lequesne score were considered and overall safety of the injection themselves . RESULTS The mean age of the patients was 63.6 years . Treatment with PRGF-Endoret was significantly more efficient than treatment with Durolane HA in reducing knee pain and stiffness and improving physical function in patients with knee OA . The rate of response to PRGF-Endoret was significantly higher than the rate of response to HA for all the scores including pain , stiffness , and physical function on the WOMAC , Lequesne index , and OMERACT-OARSI responders at 24 and 48 weeks . Adverse events were mild and evenly distributed between the groups . CONCLUSIONS Our findings show that PRGF-Endoret is safe and significantly superior to Durolane HA in primary and secondary efficacy analysis both at 24 and 48 weeks ; provides a significant clinical improvement , reducing patients ' pain and improving joint stiffness and physical function with respect to basal levels in patients with knee OA ; and should be considered in the treatment of patients with knee OA PURPOSE OF THE STUDY There is increasing use of platelet-rich plasma ( PRP ) in orthopaedics as it is a simple , cheap and minimally invasive technique . This study aim ed to compare the effects of the use of PRP and hyaluronic acid ( HA ) injections in the knee of patients diagnosed with and being followed-up for degenerative arthritis . MATERIAL S AND METHODS This prospect i ve study included 90 patients with complaints of knee pain with findings of mild or moderate degenerative arthritis . In the PRP group ( n=45 ) , one intra-articular injection was applied and in the HA group ( n=45 ) , three doses of intra-articular injection were applied . Clinical evaluation was made by Knee Injury and Osteoarthritis Outcome Score ( KOOS ) and a visual pain scale . RESULTS No severe adverse events was observed . Statistically significant better results in the KOOS score and visual pain scale was determined in PRP group than HA group at 3 months and 6 months follow up . The cost of the application for the PRP group was lower than that of the HA group . CONCLUSION The results of this study have shown the application of single dose PRP to be a safe , effective and low-cost method for treating OA . However , further studies are required for a more clear result Background : Specific growth factors have been proposed as therapeutic proteins for cartilage repair . Hypothesis : Platelet-rich plasma ( PRP ) provides symptomatic relief in early osteoarthritis ( OA ) of the knee . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 78 patients ( 156 knees ) with bilateral OA were divided r and omly into 3 groups . Group A ( 52 knees ) received a single injection of PRP , group B ( 50 knees ) received 2 injections of PRP 3 weeks apart , and group C ( 46 knees ) received a single injection of normal saline . White blood cell (WBC)–filtered PRP with a platelet count 3 times that of baseline ( PRP type 4B ) was administered in all . All the groups were homogeneous and comparable in baseline characteristics . Clinical outcome was evaluated using the Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) question naire before treatment and at 6 weeks , 3 months , and 6 months after treatment . They were also evaluated for pain by a visual analog scale , and overall satisfaction with the procedure and complications were noted . Results : Statistically significant improvement in all WOMAC parameters was noted in groups A and B within 2 to 3 weeks and lasting until the final follow-up at 6 months , with slight worsening at the 6-month follow-up . The mean WOMAC scores ( pain , stiffness , physical function , and total score ) for group A at baseline were 10.18 , 3.12 , 36.56 , and 49.86 , respectively , and at final follow-up were 5.00 , 2.10 , 20.08 , and 27.18 , respectively , showing significant improvement . Similar improvement was noted in group B ( mean WOMAC scores at baseline : 10.62 , 3.50 , 39.10 , and 53.20 , respectively ; mean WOMAC scores at final follow-up : 6.18 , 1.88 , 22.40 , and 30.48 , respectively ) . In group C , the mean WOMAC scores deteriorated from baseline ( 9.04 , 2.70 , 33.80 , and 45.54 , respectively ) to final follow-up ( 10.87 , 2.76 , 39.46 , and 53.09 , respectively ) . The 3 groups were compared with each other , and no improvement was noted in group C as compared with groups A and B ( P < .001 ) . There was no difference between groups A and B , and there was no influence of age , sex , weight , or body mass index on the outcome . Knees with Ahlback grade 1 fared better than those with grade 2 . Mild complications such as nausea and dizziness , which were of short duration , were observed in 6 patients ( 22.2 % ) in group A and 11 patients ( 44 % ) in group B. Conclusion : A single dose of WBC-filtered PRP in concentrations of 10 times the normal amount is as effective as 2 injections to alleviate symptoms in early knee OA . The results , however , deteriorate after 6 months . Both groups treated with PRP had better results than did the group injected with saline only
PURPOSE The goal of this study was to systematic ally review the efficacy and safety of plasma rich in growth factors ( PRGF ) as a treatment for reducing symptoms in patients with knee osteoarthritis .