Research Studies: Knee Arthritis


Knee Arthritis    



Treatment with adipose stem cells with arthroscopy before and after treatment  (2014)

Information about this study, as well as Dr. Reeves' commentary on the study, are provided with this PDF file.



Randomized trial of dextrose injection versus saline injection versus exercise  (2013)

Information about this study, as well as Dr. Reeves' commentary on the study, are provided with this PDF file.



Randomized crossover trial of dextrose injection versus exercise  (2012)

Information about this study, as well as Dr. Reeves' commentary on the study, are provided with this PDF file.



One-Year Follow-Up on 15% dextrose outside and 25% dextrose inside the knee (2012)

 Hypertonic dextrose injections (prolotherapy) for knee osteoarthritis: results of a single-arm uncontrolled study with 1-year follow-up. J Altern Complement Med. 2012 Apr;18(4):408-14. Department of Family Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53715, USA.

The abstract is available here...

OBJECTIVE: The objective of this study was to determine whether prolotherapy, an injection-based complementary treatment for chronic musculoskeletal conditions, improves pain, stiffness, and function in adults with symptomatic knee osteoarthritis (KOA) compared to baseline status.

DESIGN: This was a prospective, uncontrolled study with 1-year follow-up.

SETTING: The study was conducted in an outpatient setting.

PARTICIPANTS: Adults with at least 3 months of symptomatic KOA, recruited from clinical and community settings, participated in the study.

INTERVENTIONS: Participants received extra-articular injections of 15% dextrose and intra-articular prolotherapy injections of 25% dextrose at 1, 5, and 9 weeks, with as-needed treatments at weeks 13 and 17.

OUTCOME MEASURES:  Primary outcome measure was the validated Western Ontario McMaster University Osteoarthritis Index (WOMAC). Secondary outcome measure was the validated Knee Pain Scale (KPS). Tertiary outcome measure was procedure-related pain severity and participant satisfaction.

RESULTS: Thirty-six (36) participants (60 ± 8.7 years old, 21 female) with moderate-to-severe KOA received an average of 4.3 ± 0.7 prolotherapy injection sessions over a 17-week treatment period and reported progressively improved scores during the 52-week study on WOMAC and KPS measures. Participants reported overall WOMAC score improvement 4 weeks after the first injection session (7.6 ± 2.4 points, 17.2%), and continued to improve through the 52-week follow-up (15.9 ± 2.5 points, p<0.001, 36.1%). KPS scores improved in both injected (p<0.001) and uninjected knees (p<0.05). Prescribed low-dose opioid analgesia effectively treated procedure-related pain. Satisfaction was high and there were no adverse events. Female gender, age 46-65 years old, and body-mass index of 25 kg/m(2) or less were associated with greater improvement on the WOMAC instrument.

CONCLUSIONS: In adults with moderate to severe KOA, dextrose prolotherapy may result in safe, significant, sustained improvement of knee pain, function, and stiffness scores. Randomized multidisciplinary effectiveness trials including evaluation of potential disease modification are warranted to further assess the effects of prolotherapy for KOA.



Randomized Crossover Study of RIT in Knee OA 15% dextrose in colllateral ligaments and 20% in the knee (2012)

Dumais R, Benoit C, Dumais A, Babin L, Bordage R, de Arcos C, Allard J, Bélanger M.  Effect of Regenerative Injection Therapy on Function and Pain in Patients with Knee Osteoarthritis: A Randomized Crossover Study.  Pain Med. 2012 Jul 3. doi: 10.1111/j.1526-4637.2012.01422.x. [Epub ahead of print]

Dr. Georges-L.-Dumont Regional Hospital, Vitalité Health Network, Moncton, New Brunswick Centre de formation médicale du Nouveau-Brunswick, Moncton, New Brunswick Dieppe Family Medicine Unit, Dieppe, New Brunswick Department of Family Medicine, Université de  Sherbrooke, Sherbrooke, Quebec Department of Mathematics and Statistics, Université de Moncton, Moncton, New Brunswick Research Centre,  Vitalité Health Network, Moncton, New Brunswick, Canada.


The abstract is available here...

OBJECTIVE:  We assessed the effectiveness of regenerative injection therapy (RIT) to relieve pain and restore function in patients with knee osteoarthritis.

DESIGN: Crossover study where participants were randomly assigned to receive exercise therapy for 32 weeks in combination with RIT on weeks 0, 4, 8, and 12 or RIT on weeks 20, 24, 28, and 32.

PATIENTS: Thirty-six patients with chronic knee osteoarthritis.

INTERVENTIONS: RIT, which is made up of injections of 1 cc of 15% dextrose 0.6% lidocaine in the collateral ligaments and a 5 cc injection of 20% dextrose 0.5% lidocaine inside the knee joint.

OUTCOME MEASURES:  The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index of severity of osteoarthrosis symptoms (WOMAC) score (range: 0-96).

RESULTS:  Following 16 weeks of follow-up, the participants assigned to RIT presented a significant reduction of their osteoarthritis symptoms
(mean ± standard deviation: -21.8 ± 12.5, P < 0.001). WOMAC scores in this group did not change further during the last 16 weeks of follow-up, when the participants received exercise therapy only (-1.2 ± 10.7, P = 0.65). WOMAC scores in the first 16 weeks did not change significantly among the participants receiving exercise therapy only during this period (-6.1 ± 13.9, P = 0.11). There was a significant decrease in this groups' WOMAC scores during the last 16 weeks when the participants received RIT (-9.3 ± 11.4, P = 0.006). After 36 weeks, WOMAC scores improved in both groups by 47.3% and 36.2%. The improvement attributable to RIT alone corresponds to a 11.9-point (or 29.5%) decrease in WOMAC scores.

CONCLUSIONS:  The use of RIT is associated with a marked reduction in symptoms, which was sustained for over 24 weeks.
Wiley Periodicals, Inc.



Osteoarthritis of Knee PRP Kon et al (2009)

Kon E, Buda R, Filardo G, Di Martino A, Timoncini A, Canacchi A, Fornasari PM, Giannini S, Marcacci M. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc 2010; 18(4):472-479.

Dr. Reeves' Notes:  PRP was utilized X 3 for patients with moderate knee arthritis with good results for 6 months and then slowly recurring symptoms. Blood was drawn and samples prepared and frozen and then thawed for 2nd and 3rd injections. This study was a safety study showing results in 115 knees. Knees with degenerative chrondropathy did better than those with early OA and those with advanced OA clearly did not do as well. 

The abstract is available here, with a copy of the content below...

Abstract 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 clinically prospectively 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.



Osteoarthritis: Stem Cell Use: Case Report Centeno (2008)

Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician (United States), May-Jun 2008, 11(3) p343-53

Dr. Reeves' Notes: 200 ml of blood was drawn from a single patient and spun down to provide platelet rich plasma to support the bone marrow cultures. 10 ml of L post sup iliac spine (PSIS) marrow was obtained and 10 ml of R PSIS marrow in an operating room.  5 passages (culture method with 5 periods of growth to allow enough stem cells to be obtained) were taken to separate and concentrate the MSCs (mesenchymal stem cells or cells that can become ligament, tendon and cartilage cells). Bone marrow aspiration is performed again to obtain 1 ml of fresh nucleated cells, and blood is drawn for a fresh platelet rich plasma component with the latter diluted to 10% platelet solution. The cultured and grown MSCs are injected along with the 1 ml of nucleated cells and 1 ml of platelets into the knee .  1 ml of dilute (10%) platelets were then injected in the knee one week after stem cell injection. 1 ml of dilute (10%) platelets were then injected in the knee two weeks after stem cell injection.

Analysis: In summary the interventions taken included 3 bone marrow aspirations, 4 blood draws for platelet rich plasma, and 3 knee injections. In addition there was a time lag for culture prep and passages of MSCs. This is a lot of interventions and expense, of course. Nevertheless this is an excellent study in that it explains the process with the best of current technology and this was a 6 month followup. Notice that the patient in this study appeared to have some cartilage left.

A PDF version of the study is available here.

An abstract is available here, with a copy of the content below...

BACKGROUND: The ability to repair tissue via percutaneous means may allow interventional pain physicians to manage a wide variety of diseases including peripheral joint injuries and osteoarthritis. This review will highlight the developments in cellular medicine that may soon permit interventional pain management physicians to treat a much wider variety of clinical conditions and highlight an interventional case study using these technologies

OBJECTIVE: To determine if isolated and expanded human autologous mesenchymal stem cells could effectively regenerate cartilage and meniscal tissue when percutaneously injected into knees.

DESIGN: Case Study

SETTING: Private Interventional Pain Management practice.

METHODS: An IRB approved study with a consenting volunteer in which mesenchymal stem cells were isolated and cultured ex-vivo from bone marrow aspiration of the iliac crest. The mesenchymal stem cells were then percutaneously injected into the subject's knee with MRI proven degenerative joint disease. Pre- and post-treatment subjective visual analog pain scores, physical therapy assessments, and MRIs measured clinical and radiographic changes.

RESULTS: At 24 weeks post-injection, the patient had statistically significant cartilage and meniscus growth on MRI, as well as increased range of motion and decreased modified VAS pain scores.

CONCLUSION: The described process of autologous mesenchymal stem cell culture and percutaneous injection into a knee with symptomatic and radiographic degenerative joint disease resulted in significant cartilage growth, decreased pain and increased joint mobility in this patient. This has significant future implications for minimally invasive treatment of osteoarthritis and meniscal injury.



Osteoarthritis of Knee DEX Reeves et al (2000) -- 10% dextrose versus hypotonic lidocaine in advanced Knee OA

Reeves KD Hassanein K Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Alt Ther Hlth Med 2000;6(2):37-46.

Dr. Reeves' Notes:  In this study of patients with advanced knee osteoarthritis (bone on bone on skier's view in 35/111 knees), the 10% dextrose injection was superior to the hypotonic lidocaine solution injection, (p =0.15) showing better results in walking pain (35%), subjective swelling(45%), a 67% reduction in knee buckling episodes, and a substantial (13 degree) improvement in active knee bending ability. It is important to note that the control solution (0.1% lidocaine) was not likely a placebo because injection resulted in 26% improvement in walking pain and a 7.7 degree increase in goniometrically measured knee range of motion. Hypotonic solutions have effects on growth factors too, and tonicity of control solutions should be considered in study designs. 

Subjects had chronic knee pain (6 months minimum with an average of 8 years). The average cartilage thickness was only 3 mm on skier's view (medial compartment primarily) The treatment consisted of 3 injections of 9 cc of 10% dextrose solution over 6 months versus an identical volume hypotonic lidocaine solution.

Note the "control" solution, chosen for maximum safety in human subject committee submission was bacteriostatic water with low dose (0.1%) lidocaine). This calculated osmolarity is 105 mOsm, and less than 250 mOsm we now know affects growth factors and may not be a placebo.

A PDF of the study is available here.

The abstract is available here, with a copy below...

Context: Prolotherapy in arthritis Objective: Determine the effects of injection of hypertonic dextrose on knee osteoarthritis.

Design: Prospective randomized double-blind controlled trial.

Setting: Outpatient physical medicine clinic. Patients or other participants: 6 months or more of pain and either grade 2 or 3 joint narrowing or grade 2 or 3 osteophyte in any knee compartment.

Intervention: Three bimonthly injections of 9 c.c. of either 10% Dextrose and .075% Xylocaine in bacteriostatic water (active solution) versus an identical control solution absent 10% Dextrose. The dextrose-treated joints then received 3 further bimonthly injections of 10% dextrose in open-label fashion.

Main Outcome Measures: 100 mm visual analogue scale (V.A.S.) for rest pain, walking pain, standing pain, and swelling. The number of buckling episodes were estimated over the preceding two months. Flexion was goniometrically measured in blinded fashion. Radiographic measures of cartilage thickness, osteophyte grade, and hypertrophic change were obtained.

Results: The magnitude of improvement in subjective and objective measures in control-treated knees suggested that the control solution (water) may have had more than a placebo effect. Nevertheless, Hotelling multivariate analysis of paired observations between 0 and 6 months for pain, swelling, buckling episodes, and flexion revealed significantly more benefit from the dextrose injection, (p = .015 ). By 12 months (6 injections) the dextrose-treated knees improved in pain, swelling, knee buckling and flexion by 44%, 63%, 85% and 14 degrees respectively. Analysis of blinded radiographic readings of 0 and 12 month films revealed a statistically significant improvement in radiographic measures of osteoarthritis from 0 to 12 months.

Conclusion: Prolotherapy (Injection to produce a growth or repair response in body cells) utilizing sub-inflammatory levels of dextrose (10%) solution, when performed bimonthly, resulted in clinically and statistically significant improvements in knee osteoarthritis. Blinded radiographic follow up at 1 year suggests improvement in several measures of osteoarthritic severity.


K. Dean Reeves, M.D. is a physician and medical researcher in the area of pain caused by arthritis, chronic sprains and chronic strains. His private practice is located in the greater Kansas City area of Roeland Park, Kansas.  He collaborates in research with other locations across the country and internationally, and is licensed in the states of Kansas and Missouri.

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Copyright 2011-2014
Dr. K. Dean Reeves

No part of this site should be understood to be personal medical advice or instruction in how to perform injection therapy. A decision on treatment requires a good history and full examination and a knowledge of your treatment goals. Treatment decisions should be made in consultation with your personal healthcare professional and/or prolotherapist.