Prolotherapy: Under-Recognized Treatment for Osteoarthritis Pain

Pain in Osteoarthritis

by Barbara Woldin, BS, and Ross Hauser, MD

Prolotherapy, also known as proliferative therapy, regenerative injection therapy, or platelet rich plasma (PRP) therapy, is emerging as a promising treatment option for musculoskeletal and arthritic pain. Prolotherapy injections target multiple potential pain generators in and around painful joints and are typically administered into joints and surrounding ligaments of the spine, pelvis, and peripheral joints to tighten unstable joints. Prolotherapy has shown success in a number of case series, including patients with diagnosed OA (6, 27-39).

In Hackett-Hemwall prolotherapy, a small amount of a proliferant solution such as hypertonic dextrose, sodium morrhuate, or polidocanol is injected into the painful entheses of ligaments or tendons, as well as at trigger points and adjacent joint spaces. This produces an inflammatory response involving fibroblastic and capillary proliferation, along with growth factor stimulation, that induces healing and strengthening of the damaged or diseased structure (40-42). When OA is advanced, cellular prolotherapy, which utilizes cellular and extracellular matrix components of the blood, fat, or bone marrow, is recommended. This cell-based technique consists of intra-articular injections of the PRP portion of the blood or progenitor cells from a lipoaspirate or bone marrow aspiration (43). The goal of this type of prolotherapy treatment is not only pain relief but also regeneration of joint structures including articular cartilage.

Prolotherapy has shown success in alleviating pain and improving function in OA (31,44-47). Rabago and his group recently conducted two studies, one a single-arm uncontrolled study (44) and another, a three-arm randomized controlled trial (RCT) (45), using dextrose prolotherapy in the treatment of symptomatic chronic knee OA. In the single-arm trial, they compared pain and disability scores for participants before and after receiving prolotherapy; in the randomized controlled trial, they compared the effects of prolotherapy with blinded saline control or at-home exercise therapy. Outcomes in both studies showed significant improvements in WOMAC scores at one year post treatment compared to baseline; in the RCT, knee pain scale scores in the dextrose prolotherapy group were also significant compared to at-home exercise or saline-control injections. Reeves and Hassanein (46,47) previously conducted two prospective, randomized, double-blind, placebo controlled trials that showed the efficacy of dextrose prolotherapy in relieving OA pain. In a knee OA study, dextrose prolotherapy resulted in statistically and clinically significant improvements in pain, swelling, buckling, and flexion range of motion at six months, as compared with a control solution, according to Visual Analogue Score ratings (46). In a finger/thumb OA study (47), participants assigned to prolotherapy treatment achieved significant improvement in pain with movement of fingers, compared with the control group.

Overall, dextrose prolotherapy treatment, as reported in these studies, resulted in safe, significant, and sustained improvements in quality-of-life, function, stiffness, and pain measures for OA. Studies using cellular proliferants for prolotherapy have also demonstrated efficacy in OA. In one study of patients with knee OA, PRP prolotherapy significantly improved pain, function, stiffness, and quality of life at six months following intra-articular infiltration of plasma rich in growth factors (PGRF) (48). These results were confirmed in a separate study involving 115 knees with articular degeneration in which significant improvements in pain, function, and quality of life were documented at 6 and 12 months following treatment (49). Another study involving 15 knees showed no change in MRIs, although statistically significant changes in pain, function, and activities of daily living were observed at one year (50).

More recent research in prolotherapy has involved the use of mesenchymal stem cells (MSCs) from adipose tissue and bone marrow, which can differentiate into various connective tissue types including cartilage (51-53). While no RCTs have been conducted, smaller studies using autologous bone marrow MSCs had positive outcomes; overall improvements in pain, functional status of the knee, and walking ability, as well as in cartilage quality, were reported (54,55). In our own clinic, intra-articular autologous bone marrow injections in combination with dextrose prolotherapy showed statistically significant improvements in VAS scores, stiffness, and range of motion, even in patients with severe OA who had been advised to have joint replacement surgery (6,56).


  • 6 – Hauser R, Woldin B. Treating osteoarthritic joints using dextrose prolotherapy and direct bone marrow aspirate injection therapy. Open Arthritis J. 2014;7:1-9
  • 27 – Kim SR, Stitik TP, Foye PM, Greenwald BD, Campagnolo DI. Critical review of prolotherapy for osteoarthritis, low back pain and other musculoskeletal conditions: a physiatric perspective. Am J Phys Med Rehabil. 2004;83(5):379-89
  • 28 – Kim JM. The effect of prolotherapy for osteoarthritis of the knee. J Korean Acad Rehabil Med. 2002;26(4):445-448.
  • 29 – Hackett GS, Huang TC, Raftery A, Dodd TJ. Back pain following trauma and disease-prolotherapy. Milit Med. 1961;126:517-525.
  • 30 – Hackett, G. Low back pain. Brit J Phys Med. 1956;19(2):25-35.
  • 31 – Jo D, Ryu K, Yang S, Kim M. The effects of prolotherapy on shoulder pain. Korean J Anesthesiol. May 2004;46(5):589-592.
  • 32 – Hauser R, Hauser M, Holian P. Hackett-Hemwall dextrose prolotherapy for unresolved elbow pain. Pract Pain Manage. 2009;9(8):14-26.
  • 33 – Hooper RA, Frizzell JB, Faris P. Case series on chronic whiplash related neck pain treated with intraarticular zygapophysial joint regeneration injection therapy. Pain Physician. 2007;10(2):313-318.
  • 34 – Centeno CJ, Elliott J, Elkins WL, Freeman M. Fluoroscopically guided cervical prolotherapy for instability with blinded pre and post radiographic reading. Pain Physician. 2005;8(1):67-72
  • 35 – Hakala RV. Prolotherapy (proliferation therapy) in the treatment of TMD. Cranio. 2005;23(4):283-288.
  • 36 – Schultz LW. A treatment for subluxation of the temporomandibular joint. JAMA. 1937;109(13):1032-1035.
  • 37 – Reeves KD, Topol GA, Fullerton BD. Evidence-based regenerative injection therapy (prolotherapy) in sports medicine. In Seidenberg PH, Beutler PI. (Eds). The Sports Medicine Resource Manual. Saunders (Elsevier); 2008:611-619.
  • 38 – Hackett, G. Shearing injury to the sacroiliac joint. J Int Coll Surg. 1954;22:631-642.
  • 39 – Cusi M, Saunders J, Hungerford B, Wisbey-Roth T, Lucas P, Wilson S. The use of prolotherapy in the sacroiliac joint. Br J Sports Med. Feb 2010;44(2):100-104.
  • 40 – Maynard J, Pedrini VA, Pedrini-Mille A, Romanus B, Ohlerking F. Morphological and biomechanical effects of sodium morrhuate on tendons. J Orthop Res. 1985;3(2):236-48.
  • 41 – Hackett G. Joint stabilization: an experimental, histologic study with comments on the clinical application in ligament proliferation. Am J Surg. 1955;89(5):968-973.
  • 42 – Kim HJ, Kim SH, Yun DH, Lee KS, Jeong TS. The effects of anti-inflammatory drugs on histologic findings of the experimental prolotherapy model. J Korean Acad Rehabil Med. 2006;30(4):378-384.
  • 43 – Hauser RA, Maddela HS, Alderman D, et al. Journal of Prolotherapy International Medical Editorial Board consensus statement on the use of prolotherapy for musculoskeletal pain. J Prolotherapy. 2011;3(4):744-764.
  • 44 – Rabago D, Zgierska A, Fortney L, et al: Hypertonic dextrose injections (prolotherapy) for knee osteoarthritis: results of a single-arm uncontrolled study with 1-year follow-up. J Altern Complement Med. 2012;18(4):408-414.
  • 45 – Rabago D, Patterson JJ, Mundt M, et al: Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Ann Fam Med. 2013;11(3):229-237.
  • 46 – Reeves KD, Hassanein KM. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med. 2000;6(2):68-74, 77-80.
  • 47 – Reeves KD, Hassanein KM. Randomized, prospective, placebo-controlled double-blind study of dextrose prolotherapy for osteoarthritic thumb and finger (DIP, PIP, and trapeziometacarpal) joints: evidence of clinical efficacy. J Altern Complement Med. 2000;6(4):311-20.
  • 48 – Wang-Saegusa A, Cugat R, Ares O, Seijas R, Cuscó X, Garcia-Balletbó M. Infiltration of plasma rich in growth factors for osteoarthritis of the knee short-term effects on function and quality of life. Arch Orthop Trauma Surg. 2011;131(3):311-317.
  • 49 – Kon E, Buda R. Filardo G, et al. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc. 2010;18(4):472-479.
  • 50 – Halpern B, Chaudhury S, Rodeo S, et al. Clinical and MRI outcomes after platelet-rich plasma treatment for knee osteoarthritis. Clin J Sport Med. 2013;23(3):238-239.
  • 51 – Sampson S, Botto-van Bemden A, Aufiero D. Autologous bone marrow concentrate: review and application of a novel intra-articular orthobiologic for cartilage disease. Phys Sportsmed. 2013;41(3):7-18.
  • 52 – Hauser RA, Eteshola E. Rationale for using direct bone marrow aspirate as a proliferant for regenerative injection therapy (prolotherapy). Open Stem Cell J. 2013;4:7-14.
  • 53 – Alexander RW. Autologous fat grafts as mesenchyma stromal stem cell source for use in prolotherapy: a simple technique to acquire lipoaspirants. J Prolotherapy. 2011;3(3):680-688.
  • 54 – Emadedin M, Aghdami N, Taghiyar L, et al. Intra-articular injection of autologous mesenchyma stem cells in six patients with knee osteoarthritis. Arch Iran Med. 2012;15(7):422-428.
  • 55 – Orozco L, Munar A, Soler R, et al. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation. 2013;95(12):1535-1541.
  • 56 – Hauser R, Orlofsky A. Regenerative injection therapy with whole bone marrow aspirate for degenerative joint disease: a case series. Clin Med Insights: Arthritis Musculoskel Disord. 2013;6:65-72.


Ross A. Hauser, MD is board certified in physical medicine and rehabilitation and is the medical director of Caring Medical and Rehabilitation Services, with offices in Oak Park, Illinois and Fort Myers, Florida. For over 20 years, Dr. Hauser has specialized in the treatment of chronic pain, arthritis, and sports injuries with dextrose Prolotherapy, in addition to Stem Cell Therapy and Platelet Rich Plasma. He has authored 7 books on the subject of Prolotherapy, as well as published numerous scientific articles on Prolotherapy and other pain treatments. Dr. Hauser is also a lecturer and instructor on regenerative injection techniques and natural health.

Barbara Woldin, has a B.S. in journalism and an A.S. in chemistry, She has over 25 years of experience in science communicattions and has authored a dozen or
more articles and one book.

From The Pain Practitioner, Fall 2014. Join the Academy to receive The Pain Practitioner.