Prolotherapy

A 2015 review found no evidence that prolotherapy is safe or effective for Achilles tendinopathy, plantar fasciosis, and Osgood–Schlatter disease. The quality of the studies was also poor.{{cite journal |last1=Sanderson |first1=LM |last2=Bryant |first2=A |title=Effectiveness and safety of prolotherapy injections for management of lower limb tendinopathy and fasciopathy: a systematic review.|journal=Journal of Foot and Ankle Research| volume=8| pages=57| year=2015| doi=10.1186/s13047-015-0114-5|pmid=26500703 |pmc=4617485 |doi-access=free }} Another 2015 review assigned a strength of recommendation level A for Achilles tendinopathy and knee osteoarthritis and level B for lateral epicondylosis, Osgood–Schlatter disease, and plantar fasciosis.{{cite journal |last1=Covey |first1=CJ |last2=Sineath |first2=MH Jr |last3=Penta |first3=JF |last4=Leggit |first4=JC |title=Prolotherapy: Can it help your patient? |journal=Journal of Family Practice |volume=64 |issue=12 |pages=763–768 |year=2015|pmid=26844994}} Level A recommendations are based on consistent and good-quality patient-oriented evidence while level B are based on inconsistent or limited-quality patient-oriented evidence.

A 2007 Cochrane review of prolotherapy in adults with chronic low-back pain found unclear evidence of effect.{{cite journal |doi=10.1002/14651858.CD004059.pub3 |pmid=17443537|title=Prolotherapy injections for chronic low-back pain |journal=Cochrane Database of Systematic Reviews |volume=34 |issue=1 |pages=49–59 |year=2007 |last1=Dagenais |first1=Simon |last2=Yelland |first2=Michael J |last3=Del Mar |first3=Chris |last4=Schoene |first4=Mark L |last5=Nelemans |first5=P |pmc=6986690|hdl=10072/26843 |s2cid=21217911 |hdl-access=free }} A 2009 review concluded the same for subacute low back pain.{{cite journal |doi=10.1097/brs.0b013e3181909558 |pmid=19127161 |title=Injection Therapy for Subacute and Chronic Low Back Pain |journal=Spine |volume=34 |issue=1 |pages=49–59 |year=2009 |last1=Staal |first1=J Bart |last2=De Bie |first2=Rob A. |last3=De Vet |first3=Henrica C. W. |last4=Hildebrandt |first4=Jan |last5=Nelemans |first5=Patty |s2cid=32221321 }} A 2015 review found consistent evidence that it does not help in low back pain. There was tentative evidence of benefit when used with other low back pain treatments. Evidence of benefit remains tentative (level B) for dextrose prolotherapy in low back or sacroiliac pain.{{cite journal |last1=Reeves |first1=KD |last2=Sit |first2=RWS |last3=Rabago |first3=D|title=Dextrose Prolotherapy: A narrative review of basic science and clinical research, and best treatment recommendations. |journal=Physical Medicine & Rehabilitation Clinics of North America |volume=27 |issue=4 |pages=783–823|year=2016|doi=10.1016/j.pmr.2016.06.001|pmid=27788902}}

A 2009 systematic review of the efficacy in the treatment of lateral epicondylitis concluded that these therapies may benefit people with lateral epicondylitis, but the evidence was limited. A 2010 review concluded moderate evidence exists to support the use of prolotherapy injections in the management of pain in lateral epicondylitis, and that prolotherapy was no more effective than eccentric exercise in the treatment of Achilles tendinopathy.{{cite journal |doi=10.1016/S0140-6736(10)61160-9 |pmid=20970844 |title=Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: A systematic review of randomised controlled trials |journal=The Lancet |volume=376 |issue=9754 |pages=1751–67 |year=2010 |last1=Coombes |first1=Brooke K |last2=Bisset |first2=Leanne |last3=Vicenzino |first3=Bill |hdl=10072/35812 |s2cid=45054853 |url=https://espace.library.uq.edu.au/view/UQ:225158/UQ225158_OA.pdf |hdl-access=free }} A 2016 review found a trend towards benefit in 2016 for lateral epicondylitis.{{cite journal |last1=Morath |first1=O |last2=Kubosch |first2=EJ |last3=Lin |first3=XB |last4=Burger |first4=C |last5=Paul|first5=C |last6= Wang |first6=ZL |last7=Kong|first7=FL |last8=Welle|first8=K |last9= Jiang |first9=ZC |last10=Kabir|first10=K |title=Injection therapies for lateral epicondylalgia: a systematic review and Bayesian network meta-analysis.|journal=British Journal of Sports Medicine|volume=50 |issue=15 | pages=900–908 |year=2016|doi= 10.1136/bjsports-2014-094387|pmid=26392595 |s2cid=39792649 }} A 2017 review found tentative evidence in Achilles tendinopathy.{{cite journal |last1=Dong |first1=W |last2=Goost |first2=H |last3=Taeymans |first3=J |last4=Zwingmann |first4=J |last5=Konstantinidis |first5=L |last6= Südkamp |first6=NP |last7=Hirschmüller |first7=A |title=The effect of sclerotherapy and prolotherapy on chronic painful Achilles tendinopathy-a systematic review including meta-analysis.|journal=Scandinavian Journal of Medicine and Science in Sports |volume=Apr 27 |issue=1 |year=2017|doi= 10.1111/sms.12898 |pmid=28449312 |pages=4–15|s2cid=31502425 }}

In 2012, a systematic review studying various injection therapies found that prolotherapy and hyaluronic acid injection therapies were more effective than placebo when treating lateral epicondylitis. Of the studies evaluated, one of ten glucocorticoid trials, one of five trials for autologous blood injection or platelet-rich plasma, one trial of polidocanol, and one trial of prolotherapy met the criteria for low risk of bias. The authors noted that few of the reviewed trials met the criteria for low risk of bias.{{cite journal |doi=10.1177/0363546512458237 |pmid=22972856 |title=Comparative Effectiveness of Injection Therapies in Lateral Epicondylitis: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials |journal=The American Journal of Sports Medicine |volume=41 |issue=6 |pages=1435–46 |year=2012 |last1=Krogh |first1=T. P. |last2=Bartels |first2=E. M. |last3=Ellingsen |first3=T. |last4=Stengaard-Pedersen |first4=K. |last5=Buchbinder |first5=R. |last6=Fredberg |first6=U. |last7=Bliddal |first7=H. |last8=Christensen |first8=R. |s2cid=25355427 }}

Tentative evidence of prolotherapy benefit was reported in a 2011 review. One 2017 review found evidence of benefit from low-quality studies.{{cite journal |last1= Krstičević |first1=M |last2= Jerić |first2=M |last3= Došenović |first3=S |last4=Jeličić Kadić |first4=A |last5=Puljak |first5=L |title=Proliferative injection therapy for osteoarthritis: a systematic review.|journal=International Orthopedics|volume=41|issue=4 |pages=671–679|year=2017|doi=10.1007/s00264-017-3422-5 |pmid=28190092 |s2cid=21684137 }} A 2017 review described the evidence as moderate for knee osteoarthritis.{{cite journal |last1=Hassan |first1=F |last2=Trebinjac | first2=S |last3=Murrell |first3=WD |last4=Maffulli |first4=N |title=The effectiveness of prolotherapy in treating knee osteoarthritis in adults: a systematic review.|journal=British Medical Bulletin|volume=122|issue=1| pages=91–108 |year=2017|doi=10.1093/bmb/ldx006|pmid=28334196 |doi-access=free }} A 2016 review found benefit but there was a moderate degree of variability between trials and risk of bias.{{cite journal |last1=Sit |first1=RW |last2=Chung |first2=VCh |last3=Reeves |first3=KD |last4=Rabago |first4=N |last5=Chan|first5=KK |last6= Chan |first6=DC |last7=Wu|first7=X |last8=Ho|first8=RS |last9= Wong |first9=SY|title=Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis.|journal=Scientific Reports|volume=6 |issue=May 5| pages=25247 |year=2016|doi=10.1038/srep25247|pmid=27146849 |pmc=4857084 |bibcode=2016NatSR...625247S }} In 2019, the American College of Rheumatology recommended against prolotherapy for knee osteoarthritis.{{cite journal |last1=Kolasinski |first1=Sharon L. |last2=Neogi |first2=Tuhina |last3=Hochberg |first3=Marc C. |last4=Oatis |first4=Carol |last5=Guyatt |first5=Gordon |last6=Block |first6=Joel |last7=Callahan |first7=Leigh |last8=Copenhaver |first8=Cindy |last9=Dodge |first9=Carole |last10=Felson |first10=David |last11=Gellar |first11=Kathleen |last12=Harvey |first12=William F. |last13=Hawker |first13=Gillian |last14=Herzig |first14=Edward |last15=Kwoh |first15=C. Kent |last16=Nelson |first16=Amanda E. |last17=Samuels |first17=Jonathan |last18=Scanzello |first18=Carla |last19=White |first19=Daniel |last20=Wise |first20=Barton |last21=Altman |first21=Roy D. |last22=DiRenzo |first22=Dana |last23=Fontanarosa |first23=Joann |last24=Giradi |first24=Gina |last25=Ishimori |first25=Mariko |last26=Misra |first26=Devyani |last27=Shah |first27=Amit Aakash |last28=Shmagel |first28=Anna K. |last29=Thoma |first29=Louise M. |last30=Turgunbaev |first30=Marat |last31=Turner |first31=Amy S. |last32=Reston |first32=James |title=2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee |journal=Arthritis & Rheumatology |date=February 2020 |volume=72 |issue=2 |pages=220–233 |doi=10.1002/art.41142|pmid=31908163 |pmc=10518852 |hdl=2027.42/153546 |s2cid=210041163 |display-authors=1|hdl-access=free }}

Contraindications for patients to receive prolotherapy injections may include:

• Local abscess
• Bleeding disorders
• Patient on anticoagulant medication
• Known allergy to prolotherapy agent
• Acute infections such as cellulitis
• Septic arthritis

Relative contraindications include:{{cn|date=November 2023}}

• Acute gouty arthritis
• Acute fracture

Patients receiving prolotherapy injections have reported generally mild side effects, including mild pain and irritation at the injection site{{cite journal | vauthors = Slattengren A, Rabago D, Zgierska A | title = Prolotherapy in Primary Care Practice | journal = Primary Care: Clinics in Office Practice | date=Mar 2010 | volume = 37 | issue = 1 | pages = 65–80 | doi=10.1016/j.pop.2009.09.013 | pmid = 20188998| pmc = 2831229 }} (often within 72 hours of the injection), numbness at the injection site, or mild bleeding. Pain from prolotherapy injections is temporary and is often treated with acetaminophen or, in rare cases, opioid medications. NSAIDs are not usually recommended due to their counter action to prolotherapy-induced inflammation, but are occasionally used in patients with pain refractory to other methods of pain control. Theoretical adverse events of prolotherapy injection include lightheadedness, allergic reactions to the agent used, bruising, infection, or nerve damage. Allergic reactions to sodium morrhuate are rare. Rare cases of back pain, neck pain, spinal cord irritation, pneumothorax, and disc injury have been reported at a rate comparable to that of other spinal injection procedures.

Prolotherapy involves the injection of an irritant solution into a joint space, weakened ligament, or tendon insertion to relieve pain. Most commonly, hyperosmolar dextrose (a sugar) is the solution used;{{cite journal |doi=10.1016/j.crad.2010.09.006 |pmid=21216330 |title=Guided interventions in musculoskeletal ultrasound: What's the evidence? |journal=Clinical Radiology |volume=66 |issue=2 |pages=140–52 |year=2011 |last1=Davidson |first1=J. |last2=Jayaraman |first2=S. }} glycerine,{{cite journal |doi=10.1016/j.ocl.2013.06.013 |pmid=24095076 |title=Lateral Epicondylitis |journal=Orthopedic Clinics of North America |volume=44 |issue=4 |pages=615–23 |year=2013 |last1=Judson |first1=Christopher H. |last2=Wolf |first2=Jennifer Moriatis }} lidocaine (a commonly used local anesthetic),{{cite web |url=https://www.wsj.com/articles/SB10001424052702304410504575560214236534310 |title=A Pinch of Sugar for Pain |first=Laura |last=Johannes |date=October 19, 2010 |work=Wall Street Journal |access-date=16 December 2012}} phenol, and sodium morrhuate (a derivative of cod liver oil extract) are other commonly used agents.{{cite journal |doi=10.1016/j.pmrj.2011.04.003 |pmid=21703585 |title=Prolotherapy: A Clinical Review of Its Role in Treating Chronic Musculoskeletal Pain |journal=PM&R |volume=3 |issue=6 |pages=S78–81 |year=2011 |last1=Distel |first1=Laura M. |last2=Best |first2=Thomas M. |s2cid=40431887 }} The injection is administered at joints, ligaments, or tendons where they connect to bone.

Prolotherapy treatment sessions are generally given every two to six weeks for several months in a series ranging from three to six or more treatments. Many patients receive treatment at less frequent intervals until treatments are rarely required, if at all.{{cite journal |last1=Banks |first1=AR |title=A Rationale for Prolotherapy |journal=Journal of Orthopaedic Medicine |volume=13 |issue=3 |year=1991 |url=http://prolotherapysandiego.com/articles/A%20RATIONALE%20FOR%20PROLOTHERAPY.pdf }}

The term originated with George S. Hackett, MD, in 1956 in a publication titled "The rehabilitation of an incompetent structure by the generation of new cellular tissue". He applied the term prolotherapy from the words "proli’" (Latin), meaning offspring, and "proliferate", meaning to produce new cells in rapid succession.{{cite book|last1=Hackett|first1=GS|title=Ligament and tendon relaxation treated by prolotherapy |year=1956|publisher=Charles C. Thomas|location=Springfield, IL}} Although the erroneous term "sclerotherapy" was utilized by some in the past to describe this treatment, it is now clear that prolotherapy does not cause scarring.{{cite book|last1=Seidenberg|first1=P|title=The Sports Medicine Resource Manual|year=2008|publisher=Elsevier|location=Philadelphia|isbn=978-1-4160-3197-0|pages=611–9}} The mechanism of prolotherapy requires further clarification.{{cite web |url=http://www.upmc.com/Services/integrative-medicine/services/Pages/prolotherapy.aspx |title=Prolotherapy |year=2012 |publisher=University of Pittsburgh Medical Center |access-date=16 December 2012}}{{cite web |url=http://www.mayoclinic.com/health/prolotherapy/AN01330 |title=Prolotherapy: Solution to low back pain? |first=Brent A. |last=Bauer|year=2012 |publisher=Mayo Clinic |access-date=16 December 2012}}{{cite book |last1=Waldman |first1=S |title=Pain Management |year=2010 |publisher=Saunders (Elsevier) |location=Philadelphia |isbn=978-1-4377-0721-2 |pages=1027–44}}{{cite news| title= Injections to Kick-Start Tissue Repair |date=7 August 2007 |quote=Prolotherapy involves a series of injections designed to produce inflammation in the injured tissue |url=https://www.nytimes.com/2007/08/07/health/07brod.html |work= New York Times | access-date= 24 July 2008| first=Jane E.| last=Brody}} It is expected to involve a number of mechanisms.{{cite journal |last1=Johnston |first1=E |last2=Emani |first2=C |last3=Kochan |first3=A |last4=Ghebrehawariat |first4=K |last5=Tyburski |first5=J |last6=Johnston |first6=M |last7=Rabago |first7=D |title=Prolotherapy agent P2G is associated with upregulation of fibroblast growth factor-2 genetic expression in vitro |journal=Journal of Experimental Orthopaedics|volume=7 |issue=1|pages=97|year=2020|doi=10.1186/s40634-020-00312-z|pmid=33280075 |pmc=7719583 |doi-access=free }}

Some major medical insurance policies view prolotherapy as an investigational or experimental therapy with an inconclusive evidence base. Consequently, they currently do not provide coverage for prolotherapy procedures.{{cite web |url=http://www.aetna.com/cpb/medical/data/200_299/0207.html |title=Clinical Policy Bulletin: Prolotherapy |year=2013 |publisher=Aetna, Inc. |access-date=12 October 2013}}{{cite web |url=https://www.unitedhealthcareonline.com/ccmcontent/ProviderII/UHC/en-US/Assets/ProviderStaticFiles/ProviderStaticFilesPdf/Tools%20and%20Resources/Policies%20and%20Protocols/Medical%20Policies/Medical%20Policies/Prolotherapy_for_Musculoskeletal_Indications.pdf |title=Prolotherapy for Musculoskeletal Indications |year=2013 |work=Medical Policy |publisher=UnitedHealthCare |access-date=12 October 2013}}{{cite web |url=http://www.bcbsnc.com/assets/services/public/pdfs/medicalpolicy/prolotherapy.pdf |title=Corporate Medical Policy |year=2013 |work=Prolotherapy |publisher=BlueCross BlueShield of North Carolina|access-date=12 October 2013}} Medicare reviewers in 1999 determined at that time that practitioners had not provided "any scientific evidence on which to base a [different] coverage decision," and so retained Medicare's current coverage policy to not cover prolotherapy injections for chronic low back pain, but expressed willingness to reconsider if presented with results of "further studies on the benefits of prolotherapy."{{cite web |url=http://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=68&NCDId=15&ncdver=1&NcaName=Prolotherapy+for+Chronic+Low+Back+Pain&IsPopup=y&bc=AAAAAAAACAAAAA%3D%3D& |title=Decision Memo for Prolotherapy for Chronic Low Back Pain) |access-date=12 October 2013 |publisher=Centers for Medicare and Medicaid Services}}

The concept of creating irritation or injury to stimulate healing has been recorded as early as Roman times when hot needles were poked into the shoulders of injured gladiators.

In 1840, French surgeon Alfred-Armand-Louis-Marie Velpeau published a paper detailing how he had injected an iodine solution into a hernia in order to create beneficial inflammation.{{cite journal |id={{ProQuest|88980623}} |last1=De Garmo |first1=W B |title=THE TREATMENT OF HERNIA BY SUBCUTANEOUS INJECTION |journal=Medical Record |volume=31 |issue=2 |date=8 January 1887 |pages=35 }} American surgeon Joseph Pancoast later wrote that he had been performing this procedure (using either iodine or cantharides) since 1836. Another early American practitioner of this method was George Heaton.

After World War 1, sclerotherapy came to be a common treatment for malformations of blood vessels and the lymphatic system. This involved injecting a therapeutic liquid to shrink them.{{Cite journal |last1=Ayyappan |first1=M K |last2=Sebastian |first2=Jithin Jagan |date=2023 |title=Origin and Evolution of Sclerotherapy for Varicose Veins |journal=Indian Journal of Vascular and Endovascular Surgery |language=en |volume=10 |issue=3 |pages=237–239 |doi=10.4103/ijves.ijves_82_23 |doi-access=free |issn=0972-0820}}

By the late 1920s, this method was used to treat hernias.{{cite journal |last1=Rice |first1=Carl O. |title=The Injection Treatment of Hernia |journal=Annals of Surgery |date=March 1937 |volume=105 |issue=3 |pages=343–350 |doi=10.1097/00000658-193703000-00004 |pmc=1390347 |pmid=17856937 }} By the late 1930s, it was also used to treat ligamentous laxity.{{cite journal |last1=Rabago |first1=D |last2=Best |first2=TM |last3=Zgierska |first3=AE|last4=Zelsig|first4=E|last5=Ryan|first5=M|last6=Crane|first6=D |title=A systematic review of four injections therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood, and platelet-rich plasma|journal=British Journal of Sports Medicine |volume=43 |issue=7 |pages=471–481 |year=2009|pmid=19028733|doi=10.1136/bjsm.2008.052761 |pmc=2755040}} In the 1950s, George S. Hackett, a general surgeon in the United States, began performing injections of irritant solutions in an effort to repair joints and hernias.{{cite journal |last1=Rabago |first1=D |last2=Slattengren |first2=A |last3=Zgierska |first3=A|title=Prolotherapy in Primary Care Practice|journal=Primary Care: Clinics in Office Practice |volume=37 |issue=1 |pages=65–80 |year=2010|pmid=20188998|doi=10.1016/j.pop.2009.09.013 |pmc=2831229}}

In 1955, Gustav Anders Hemwall became acquainted with George Hackett at an American Medical Association meeting and started practicing the technique.{{Cite web |title=Prolotherapy Frequently Asked Questions |url=https://www.ocfm.com/prolotherapy |access-date=2024-03-15 |website=Osteopathic Center for Family Medicine |language=en-US}}

Hackett coined the term "prolotherapy" for the practice, a very early appearance being in his 1956 book Ligament and Tendon Relaxation (Skeletal Disability) Treated by Prolotherapy (Fibro-Osseus Proliferation).{{Cite book |last=Hackett |first=George Stuart |url=https://books.google.com/books?id=61FsAAAAMAAJ |title=Ligament and Tendon Relaxation (skeletal Disability) Treated by Prolotherapy (fibro-osseous Proliferation): With Special Reference to Occipito-cervical and Low Back Disability, Trigger Point Pain, Referred Pain, Headache and Sciatica |date=1958 |publisher=Thomas |language=en}}{{psc|date=February 2023}}{{pn|date=February 2023}}

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{{Reflist|30em}}

Category:Musculoskeletal system

Category:Orthopedic surgical procedures

Category:Regenerative biomedicine

Category:Alternative medical treatments