Prolotherapy for knee osteoarthritis | Recent research

This article highlights:

  • Prolotherapy research shows significant improvement in selected patients with knee osteoarthritis.
  • Treating the whole knee as opposed to selective parts of the knee is more effective.

Research on the benefits of Prolotherapy for knee osteoarthritis

In the latest research from June 2017, doctors publishing in the British Medical Bulletin reviewed  and evaluated Prolotherapy findings and determined Prolotherapy treatments for patients with knee osteoarthritis showed significant improvement in scores for pain, function and range of motion, both in the short term and long term. Patient satisfaction was also high in these patients (82%). 13

Recent independent research published in the doctors writing in the journal Therapeutic advances in musculoskeletal disease, says that Prolotherapy treatments in female patients with knee osteoarthritis resulted in significant improvement in pain, function, and range-of-motion scores.1

Doctors took 24 female patients with an average age of 58 (the youngest being 46 the oldest 70) and gave them three monthly Prolotherapy injections.

At the end of week 24 of the study, knee range of motion increased, pain severity in rest and activity decreased. Improvements of all parameters were considerable until week 8, and were maintained throughout the study period.

  • In new research, doctors from the University of Wisconsin School of Medicine and Public Health write: Systematic review, including meta-analysis, and randomized controlled trials suggest that Prolotherapy may be associated with symptom improvement in mild to moderate symptomatic knee osteoarthritis and overuse tendinopathy.
    • A growing body of literature suggests that prolotherapy for knee osteoarthritis may be appropriate for the treatment of symptoms associated with knee osteoarthritis in carefully selected patients who did not respond to conservative therapy.12
  • In another new study, published in the journal Scientific reports doctors in Hong Kong found that three to five sessions of Prolotherapy knee injections have a statistically significant and clinically relevant effect in the improvement of WOMAC composite score, (a scoring system of pain, function, and stiffness) at 12 to 16 weeks compared to formal at-home exercise. The benefits of the treatment were sustained up to 1 year.2
  • In another study lead by University of Wisconsin School of Medicine and Public Health researchers, patients reported substantially improved knee-specific effects, resulting in improved quality of life and activities of daily living.3 Confirming earlier research on long-term benefits of Prolotherapy for knee osteoarthritis patients.8
  • This followed an earlier combined study from the University’s researchers who along with The University of Kansas, Department of Physical Medicine and Rehabilitation (K.Dean Reeves, MD) and researchers in Hong Kong who suggested that Prolotherapy offered “positive and significant beneficial effect in the treatment of knee osteoarthritis.”4 This research was a continuation of nearly two decades of research published by Dr. Reeves on Prolotherapy and knee osteoarthritis.9,10 
  • Earlier in 2016 the Universities of Wisconsin, Kansas, and Michigan team with doctors from Argentina is publishing combined research on the positive clinical and chondrogenic (cartilage growing) effects of Prolotherapy in participants with symptomatic grade IV knee osteoarthritis.5 This suggested a disease-modifying effect or a “reversal” of the disease progression.
  • This agrees with research from 2012 which suggested adults with moderate to severe knee osteoarthritis, Prolotherapy injections may result in safe, significant, sustained improvement of knee pain, function, and stiffness scores.6,7

In November 2016, Dr. Reeves and colleagues wrote in PM & R : the journal of injury, function, and rehabilitation:

Dextrose injection is reported to improve knee osteoarthritis −related clinical outcomes, but its effect on articular cartilage is unknown. A chondrogenic effect of dextrose injection has been proposed.  This study assessed biological and clinical effects of intra-articular hypertonic dextrose injections (prolotherapy) in painful knee osteoarthritis.

The study design was case series with blinded arthroscopic evaluation before and after treatment.

Study Participants
Symptomatic knee osteoarthritis for at least 6 months, arthroscopy-confirmed medial compartment exposed subchondral bone (a bone on bone situation), and temporary pain relief with intra-articular lidocaine injection.

Intervention
Four to 6 monthly 10-mL intra-articular injections with 12.5% dextrose.

Results

  • Six participants (1 female and 5 male) with median age of 71 years, and avergage 9-year pain duration
  • WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) a pain measurement scoring system) composite score of 57.5 points, signifying problems with pain, stiffness, and function.
  • Patients received an average of 6 dextrose injections and follow-up arthroscopy at 7.75 months (range 4.5-9.5 months) – to measure effectiveness of treatment.
  • Posttreatment showed cartilage growth compared with the pretreatment.
  • Biopsy specimens showed metabolically active cartilage with variable cellular organization, fiber parallelism, and cartilage typing patterns consistent with fibro- and hyaline-like cartilage.
  • Compared with baseline status, the median WOMAC score improved 13 points.

Positive clinical and chondrogenic (cartilage growth) effects were seen after prolotherapy with hypertonic dextrose injection in participants with symptomatic grade IV Knee Osteoarthritis, suggesting disease-modifying effects and the need for confirmation in controlled studies. Minimally invasive arthroscopy (single-compartment, single-portal) enabled collection of robust intra-articular data.5

Prolotherapy for Knee Pain

In published research in the Journal of Prolotherapy, Ross Hauser MD investigated the outcomes of patients receiving Prolotherapy treatment for unresolved, difficult to treat knee pain at a charity clinic in  Illinois.

  • 80 patients, representing a total of 119 knees, that were treated quarterly with Prolotherapy.
  • The results of this study showed that patients had a statistically significant decline in their level of pain, stiffness, crunching sensation, and improvement in their range of motion with Prolotherapy.
  • More than 82% showed improvements in walking ability, medication usage, athletic ability, anxiety, depression, and overall disability with Prolotherapy. Ninety-six percent of patients felt Prolotherapy improved their life overall.11

Quality of Life changes after Prolotherapy treatment for knee osteoarthritis

In the same study, we asked the patients a simple yes or no question:

  • Has Prolotherapy changed your life for the better?
    • 96% of patients treated answered yes.
  • In quantifying the response,
    • 43% felt their life was at least radically better with Prolotherapy.
    • 88% rated Prolotherapy at least very successful in treating their condition (50% or greater improvement) with 50% noting the Prolotherapy to be extremely successful (75% or greater improvement).
  • The percentage of patients able to decrease their additional pain-related treatments including chiropractic, physical therapy, acupuncture, and massage after Prolotherapy was 86%.
  • The percentage of patients able to decrease their medication usage by 50% or more was 90%.

Long-term results

The patients in this study were treated four to six years prior to the publishing of this paper.

  • Eighty-seven percent noted that the results of Prolotherapy have mostly continued (at least 50% retained), and 52% of patients noted that their overall results have very much continued to the present (75% to 99%).
  • Seventy-eight percent noted there were reasons besides the Prolotherapy effect wearing off that were causing their continued pain and/or disability.
    • Of the 78%, 42% of these believe they stopped Prolotherapy too soon (before the pain was totally gone),
    • 20% re-injured the area that had received Prolotherapy,
    • 13% had a new area of pain,
    • 10% had increased life stressors, and
    • 15% had other explanations for the pain.
  • Of the patients whose pain recurred after Prolotherapy was stopped, 81% are planning on receiving more Prolotherapy.

Prolotherapy used on patients who had a duration of five years of unresolved knee pain was shown in this observational study to improve their quality of life. They reported less pain, stiffness, disability, depressed and anxious thoughts, medication and other pain therapy usage, as well as improved walking ability, range of motion, ability to work and activities of daily living. Therefore, Prolotherapy appears to be a viable treatment option for people suffering with unresolved knee pain.

Treating the whole knee

In the previously cited study above about female patients in the journal Therapeutic advances in musculoskeletal disease, researchers also noted:

  • Ignoring the patient’s other pain sources including joint-surrounding tendons and ligaments could be another potential cause of treatment failure; (in the study) we did not treat enthesopathies or the ligament fibro-osseous junctions with extra-articular dextrose injections around these elements in our study.
  • So, it appears that ligaments or other structures need to be treated to get the full benefit from prolotherapy.1

Doctors writing in the Journal of pain research have published research supporting what we have known here for decades. To most effectively treat knee osteoarthritis with Prolotherapy, Platelet Rich Plasma, or Stem Cells, you must treat the whole knee and not simply the cartilage degeneration.

In this study, doctors from the University of Tehran compared results in patients who received Prolotherapy with dextrose periarticular injections around the knee joint with patients who received Prolotherapy intra-articular injections. In other words, one group received injections around the knee joint, another group received injections directly into the knee joint.

  • Both peri- and intra-articular prolotherapy patients showed reduced pain and disability of their knee osteoarthritis after 5 months of follow-up.
  • Interestingly, periarticular prolotherapy had better effects on pain scores and disability scores in some respects.
    • Periarticular Prolotherapy injections showed superior effects on healing of knee disability and pain score compared with intra-articular injections.
    • Pain score was significantly lower at 1-, 2-, 3-, 4-, and 5-month visits in the periarticular group compared with the intra-articular group.
    • Periarticular injections have been suggested in some recent reports for analgesic effect after total knee replacement
    • Periarticular injections can significantly reduce the requirements for patient-controlled analgesia and can improve patient satisfaction following total knee replacement.
  • Periarticular injection showed adjuvant effects to intra-articular prolotherapy.

Knee function and mobility improvements

The researchers found periarticular Prolotherapy showed healing effects in many aspects of knee function that were better than with intra-articular prolotherapy. This healing effect was observed particularly in active movements, including walking on flat surfaces, and ascending and descending stairs.

More research on Prolotherapy for knee osteoarthritis

September 2016: From the University of Wisconsin School of Medicine and Public Health, a late 2016 study followed twenty-two participants treated with prolotherapy for symptomatic knee osteoarthritis who were previously enrolled in three randomized and open-label studies. At 52 weeks following enrollment, the patients were interviewed about the overall experience with Prolotherapy.

Results:

  • improvement in knee-specific quality of life was found in 18 of 22 patients. Four patients reported limited response.
  • pretreatment counseling enhanced treatment adherence and optimism of the success of the Prolotherapy treatments.
  • patients reported overall positive experience with Prolotherapy.

Conclusion:

Most participants reported substantially improved knee-specific effects, resulting in improved quality of life and activities of daily living; four participants reported minimal or no effect. Clear, complete description of procedural rationale may enhance optimism about and adherence to treatment appointments.15

Research case study | Prolotherapy as alternative to knee surgery

July 2012: A case report that was published in the medical journal Anesthesiology and Pain Medicine discusses the clinical and radiological outcomes of prolotherapy in a patient whom total knee prosthesis had been planned but surgery couldn’t be performed due to other existing medical conditions.

The patient was a 72 year old woman with severe pain at her knees for over 5 years. Treatment methods include weight loss, decreasing the weight bearing on the joint, stretching exercises, nonsteroid anti-inflammatory and steroid drugs, and physiotherapy. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale was applied to measure the osteoarthritis level of the patient: Pain level; 25 points, stiffness level; 10 points, Physical function loss; 80 points, and total WOMAC 115 points. At radiological evaluation, the patient was diagnosed as grade IV osteoarthritis due to significant osteophyte presence and complete joint space narrowing.

Six sessions of knee prolotherapy protocol was applied to the patient, one session monthly.

Significant improvement was noted at WOMAC scale (Pain level; 5 points, stiffness level; 2 points, Physical function loss; 15 points, and total WOMAC 22 points). Osteoarthritis level of the patient was improved to grade I at radiological evaluation after a year. Our case is the report that presents radiological evidence in addition to clinical findings of improvement of osteoarthritis level.

We are in the opinion that prolotherapy may be preferred more commonly as an efficient method once the importance of ligamentous structures at pathogenesis of osteoarthritis is established.16

 Knee osteoarthritis injections research:

1. Eslamian F, Amouzandeh B. Therapeutic effects of prolotherapy with intra-articular dextrose injection in patients with moderate knee osteoarthritis: a single-arm study with 6 months follow up. Ther Adv Musculoskelet Dis. 2015 Apr;7(2):35-44. [Pubmed] [Google Scholar]

2. Sit RW, Chung VC, Reeves KD, et al. Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis. Scientific Reports. 2016;6:25247. [Pubmed] [Google Scholar]

3. Rabago D, van Leuven L, Benes L, et al. Qualitative Assessment of Patients Receiving Prolotherapy for Knee Osteoarthritis in a Multimethod Study. J Altern Complement Med. 2016 Sep 7. [Pubmed] [Google Scholar]

4.  Sit RW, Chung VCh, Reeves KD, Rabago D, Chan KK, Chan DC, Wu X, Ho RS, Wong SY. Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis. Sci Rep. 2016 May 5;6:25247 [Pubmed] [Google Scholar]

5. Topol GA, Podesta LA, Reeves KD, Giraldo MM, Johnson LL, Grasso R, Jamín A, Clark T, Rabago D. Chondrogenic Effect of Intra-articular Hypertonic-Dextrose (Prolotherapy) in Severe Knee Osteoarthritis. PM R. 2016 Apr 4. pii:S1934-1482(16)30054-5. [Pubmed] [Google Scholar]

6. Rabago D, Zgierska A, Fortney L, Kijowski R, Mundt M, Ryan M, Grettie J, Patterson JJ. Hypertonic dextrose injections 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. doi: 10.1089/acm.2011.0030. [Pubmed] [Google Scholar]

7. Rabago D, Patterson JJ, Mundt M, et al. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Ann Fam Med. 2013;11(3):229–37. [Annals of family medicine] [Google Scholar]

8. Rabago D, Mundt M, Zgierska A, Grettie J. Hypertonic dextrose injection (prolotherapy) for knee osteoarthritis: long term outcomes. Complement Ther Med. 2015;23(3):388–95. [Pubmed] [Google Scholar]

9. Reeves KD, Hassanein K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med. 2000;6:68–79. [Pubmed] [Google Scholar]

10. Reeves KD, Hassanein KM. Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity. Altern Ther Health Med. 2003;9(3):58–62. [Pubmed] [Google Scholar]

11.  Hauser RA, Hauser MA.  A Retrospective Study on Dextrose Prolotherapy for Unresolved Knee Pain at an Outpatient Charity Clinic in Rural Illinois. Journal of Prolotherapy. 2009;1:11-21.

12 Rabago D, Nourani B. Prolotherapy for Osteoarthritis and Tendinopathy: a Descriptive Review. 2017 Jun;19(6):34. doi: 10.1007/s11926-017-0659-3. [Pubmed] [Google Scholar]

13 Hassan F, Trebinjac S, Murrell WD, Maffulli N. The effectiveness of prolotherapy in treating knee osteoarthritis in adults: a systematic review. Br Med Bull. 2017 Mar 4:1-18. [Pubmed] [Google Scholar]

14 Rezasoltani Z, Taheri M, Mofrad MK, Mohajerani SA. Periarticular dextrose prolotherapy instead of intra-articular injection for pain and functional improvement in knee osteoarthritis. Journal of Pain Research. 2017;10:1179-1187.  [Pubmed] [Google Scholar]

15 Rabago D, van Leuven L, Benes L, Fortney L, Slattengren A, Grettie J, Mundt M. Qualitative Assessment of Patients Receiving Prolotherapy for Knee Osteoarthritis in a Multimethod Study. J Altern Complement Med. 2016 Dec;22(12):983-989. Epub 2016 Sep 7. [Pubmed] [Google Scholar]

16 Dumais R, Benoit C, Dumais A, et al. Effect of Regenerative Injection Therapy on Function and Pain in Patients with Knee Osteoarthritis: A Randomized Crossover Study.Pain Med. 2012 Aug;13(8):990-999. doi: 10.1111/j.1526-4637.2012.01422.x. Epub 2012 Jul 3. [Pubmed] [Google Scholar]

 

 

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