Osteoarthritis medical therapy: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Osteoarthritis}} | {{Osteoarthritis}} | ||
{{CMG}} | {{CMG}}; {{AE}}[[User:DrMars|Mohammadmain Rezazadehsaatlou]][2], [[User:Irfan Dotani|Irfan Dotani]] [3]. | ||
==Overview== | ==Overview== | ||
As all diseases, the [[Osteoarthritis primary prevention|prevention]] and the early diagnosis and onetime treatment of OA play important roles patient final outcome. The treatment of OA can be categorized into two options. Treatment options of OA are: [[Osteoarthritis medical therapy|Nonsurgical]] (non-pharmacological, pharmacological, and complementary) and [[Osteoarthritis surgery|'''surgical''']] interventions. As it always was, is, and will be, the patients have this right to get the best, safest, and least invasive therapies as their first treatment options. Meanwhile, surgical interventions should be considered in patients who have responded to the first line non/less invasive therapies inadequately. Meanwhile, the [[Osteoarthritis medical therapy|non-surgical treatments]] are often effective enough as the first line in patients management. Actually, the osteoarthritis treatment is a combination of medical therapies. | |||
==Medical Therapy== | ==Medical Therapy== | ||
==== | === Non-pharmacological === | ||
Nonpharmacologic therapy is consisted of physical therapy and specific type of physical exercises, bracing and splinting:<ref name="pmid23446069">{{cite journal |vauthors=Lauche R, Cramer H, Langhorst J, Dobos G |title=A systematic review and meta-analysis of medical leech therapy for osteoarthritis of the knee |journal=Clin J Pain |volume=30 |issue=1 |pages=63–72 |date=January 2014 |pmid=23446069 |doi=10.1097/AJP.0b013e31828440ce |url=}}</ref><ref name="pmid23876571">{{cite journal |vauthors=Lauche R, Langhorst J, Dobos G, Cramer H |title=A systematic review and meta-analysis of Tai Chi for osteoarthritis of the knee |journal=Complement Ther Med |volume=21 |issue=4 |pages=396–406 |date=August 2013 |pmid=23876571 |doi=10.1016/j.ctim.2013.06.001 |url=}}</ref><ref name="pmid28121996">{{cite journal |vauthors=Zhang Y, Huang L, Su Y, Zhan Z, Li Y, Lai X |title=The Effects of Traditional Chinese Exercise in Treating Knee Osteoarthritis: A Systematic Review and Meta-Analysis |journal=PLoS ONE |volume=12 |issue=1 |pages=e0170237 |date=2017 |pmid=28121996 |pmc=5266306 |doi=10.1371/journal.pone.0170237 |url=}}</ref> | |||
* Physical therapy results in short-term pain reduction, and improvement in physical function in the diseased [[joint]] to preserve its the ability for daily tasks like walking, dressing, and even bathing. | |||
* Walking can reduce pain from osteoarthritis. A 1997 [[randomized controlled trial]] found 1 hour of walking based aerobic activity three times per week showed, over 18 months that older people with symptomatic osteoarthritis had consistent modest improvement in self-reported pain and disability compared with participation in health education programs. Futhermore, there seemed to be some correlation between increased amount of exercise and greater improvements in pain<ref name="pmid8980206">{{cite journal| author=Ettinger WH, Burns R, Messier SP, Applegate W, Rejeski WJ, Morgan T et al.| title=A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis. The Fitness Arthritis and Seniors Trial (FAST). | journal=JAMA | year= 1997 | volume= 277 | issue= 1 | pages= 25-31 | pmid=8980206 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8980206 }} </ref>. | |||
* On the other hand, resting is another important healing factor in OA. | |||
* Bracing and splinting as other methods help to support painful or unstable [[joints]]. | |||
* Using a cane can help decrease the weight pressure in diseased [[hip]] or [[knee]], but it should be used on the contralateral side of the affected joint. | |||
==== | === Analgesics === | ||
Drug therapy in OA management plays an important role in relieving pain and slow downing the progression of this disease. Meanwhile, common medications are:<ref name="pmid17636601">{{cite journal |vauthors=Watson M, Brookes ST, Faulkner A, Kirwan J |title=WITHDRAWN: Non-aspirin, non-steroidal anti-inflammatory drugs for treating osteoarthritis of the knee |journal=Cochrane Database Syst Rev |volume= |issue=1 |pages=CD000142 |date=July 2007 |pmid=17636601 |doi=10.1002/14651858.CD000142.pub2 |url=}}</ref><ref name="pmid15846645">{{cite journal |vauthors=Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, Hochberg MC, Wells G |title=Glucosamine therapy for treating osteoarthritis |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD002946 |date=April 2005 |pmid=15846645 |doi=10.1002/14651858.CD002946.pub2 |url=}}</ref><ref name="pmid16437479">{{cite journal |vauthors=Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G |title=Acetaminophen for osteoarthritis |journal=Cochrane Database Syst Rev |volume= |issue=1 |pages=CD004257 |date=January 2006 |pmid=16437479 |doi=10.1002/14651858.CD004257.pub2 |url=}}</ref> | |||
* '''[[NSAIDs|NSAIDs (Non-steroidal anti-inflammatory drugs)]]:''' Including [[acetaminophen]], [[aspirin]], [[ibuprofen]] (e.g. Advil), [[naproxen]] (e.g. Aleve), [[diclofenac]], [[cyclooxygenase-2 inhibitors]] ([[celecoxib]]-Celebrex) are used to reduce the [[inflammation]] and swelling as a common finding in OA. | |||
** Meanwhile, the [[glucosamine]] and [[chondroitin sulfate]] supplements are used in the United States as an alternative treatment for OA. For patients experiencing moderate-to-severe pain due to the knees osteoarthritis or spine osteoarthritis, they might be helpful by interacting with the diseased [[cartilage]]. | |||
* '''[[Analgesics]]:''' Including [[acetaminophen]] (e.g. [[Tylenol]]), or [[tramadol]] (e.g. Ultram) are used to reduce the pain, without any effects on [[inflammation]] or swelling. [[Analgesics]] are recommended for patients experiencing mild to moderate pain because they could cause a limited variety of side effects for patients. | |||
* '''Topical analgesics:''' These creams are usually used to reduce the pain in the diseased joint. They applied directly to the skin over the affected area. These creams consist of counterirritants (wintergreen and eucalyptus) which have a great effect on pain reduction. Capsaicin cream is derived from chili peppers and found to be effective in treating osteoarthritis pain, which can be applied as an adjunct therapy to the OA standard treatments. This group of therapies compared to NSAIDs had fewer [[Adverse effect (medicine)|adverse effects]]. | |||
{| class="wikitable" | |||
|+[[Osteoarthritis medical therapy|Medications]] Used for [[Osteoarthritis|OA]] | |||
! colspan="1" rowspan="1" |Medication | |||
! colspan="1" rowspan="1" |Typical dosage | |||
|- | |||
| colspan="1" rowspan="1" |Acetaminophen | |||
| colspan="1" rowspan="1" |650 to 1,000 mg four times per day | |||
|- | |||
| colspan="1" rowspan="1" |Celecoxib (Celebrex) | |||
| colspan="1" rowspan="1" |200 mg per day | |||
|- | |||
| colspan="1" rowspan="1" |Diclofenac sodium | |||
| colspan="1" rowspan="1" |50 mg two to three times per day | |||
|- | |||
| colspan="1" rowspan="1" |Diclofenac/misoprostol (Arthrotec) | |||
| colspan="1" rowspan="1" |50 mg/200 mcg two to three times per day | |||
|- | |||
| colspan="1" rowspan="1" |Ibuprofen, over-the-counter | |||
| colspan="1" rowspan="1" |400 to 600 mg three times per day | |||
|- | |||
| colspan="1" rowspan="1" |Meloxicam (Mobic) | |||
| colspan="1" rowspan="1" |7.5 to 15 mg per day | |||
|- | |||
| colspan="1" rowspan="1" |Nabumetone | |||
| colspan="1" rowspan="1" |500 mg two times per day | |||
|- | |||
| colspan="1" rowspan="1" |Naproxen, over-the-counter (Aleve) | |||
| colspan="1" rowspan="1" |220 to 440 mg two times per day | |||
|- | |||
| colspan="1" rowspan="1" |Naproxen (Naprosyn) | |||
| colspan="1" rowspan="1" |250 to 500 mg two times per day | |||
|- | |||
| colspan="1" rowspan="1" |Oxaprozin (Daypro) | |||
| colspan="1" rowspan="1" |1,200 mg per day | |||
|- | |||
| colspan="1" rowspan="1" |Sulindac (Clinoril) | |||
| colspan="1" rowspan="1" |150 to 200 mg two times per day | |||
|} | |||
=== | === Corticosteroids === | ||
Cortisone are a group of man-made steroids simulating the cortisol effects in body. Cortisone injections are used for two most important reasons: | |||
* '''I: Treatment option''' | |||
* '''II: Diagnostic option''' | |||
=== | ==== '''I: [[Osteoarthritis medical therapy|Treatment]]''' ==== | ||
" | Steroids (corticosteroid) have been used by injecting into the joint and reduce the inflammation, swelling, and pain in the diseased joint, for 6 weeks and 6 months period. However, studies report: | ||
* May harm knee cartilage<ref name="pmid28510679">{{cite journal| author=McAlindon TE, LaValley MP, Harvey WF, Price LL, Driban JB, Zhang M et al.| title=Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial. | journal=JAMA | year= 2017 | volume= 317 | issue= 19 | pages= 1967-1975 | pmid=28510679 | doi=10.1001/jama.2017.5283 | pmc=5815012 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28510679 }} [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=28975317 Review in: Ann Intern Med. 2017 Sep 19;167(6):JC27] </ref> | |||
* Similar effectiveness to physical therapy, but more health care usage<ref name="pmid25089860">{{cite journal| author=Rhon DI, Boyles RB, Cleland JA| title=One-year outcome of subacromial corticosteroid injection compared with manual physical therapy for the management of the unilateral shoulder impingement syndrome: a pragmatic randomized trial. | journal=Ann Intern Med | year= 2014 | volume= 161 | issue= 3 | pages= 161-9 | pmid=25089860 | doi=10.7326/M13-2199 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25089860 }} [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=25743169 Review in: Evid Based Med. 2015 Apr;20(2):67] </ref> | |||
[[ | ==== '''II: [[Osteoarthritis diagnostic criteria|Diagnostic]]''' ==== | ||
In cases having an uncertain pain especially in hip and shoulder joints, the cortisone could be helpful in reaching accurate diagnoses. For example, if after the injection the patient's hip pain decreases, this means the pain originates from the hip. However, if the hip pain persisted after injection then other problems originating from the spine or the sacroiliac joint (the spine and pelvis) could be considered as the pain sources. | |||
=== Platelet rich plasma === | |||
A [[meta-analysis]] of 6 [[randomized controlled trials]] and 4 non-randomized studies through June, 2014 found benefit for osteoarthritis of the knee<ref name="pmid25416198">{{cite journal| author=Laudy AB, Bakker EW, Rekers M, Moen MH| title=Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. | journal=Br J Sports Med | year= 2015 | volume= 49 | issue= 10 | pages= 657-72 | pmid=25416198 | doi=10.1136/bjsports-2014-094036 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25416198 }} </ref>. The meta-analysis concluded only one trial<ref name="pmid22840987">{{cite journal| author=Sánchez M, Fiz N, Azofra J, Usabiaga J, Aduriz Recalde E, Garcia Gutierrez A | display-authors=etal| title=A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. | journal=Arthroscopy | year= 2012 | volume= 28 | issue= 8 | pages= 1070-8 | pmid=22840987 | doi=10.1016/j.arthro.2012.05.011 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22840987 }} </ref> was not with high bias; however this trial does not report being registered. | |||
A more recent [[meta-analysis]] of five [[randomized controlled trial]]s published through December, 2019 found benefit compared to hyaluronic acid<ref name="pmid32278352">{{cite journal| author=Zhao J, Huang H, Liang G, Zeng LF, Yang W, Liu J| title=Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis. | journal=BMC Musculoskelet Disord | year= 2020 | volume= 21 | issue= 1 | pages= 224 | pmid=32278352 | doi=10.1186/s12891-020-03262-w | pmc=7149899 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32278352 }} </ref>. It is not clear that any of the trials were prospectively registered. | |||
[[ | |||
=== | A more recent trial, that was registered after completion, but before long term follow-up was undertaken, found no benefit compared to hyaluronic acid<ref name="pmid30545242">{{cite journal| author=Di Martino A, Di Matteo B, Papio T, Tentoni F, Selleri F, Cenacchi A | display-authors=etal| title=Platelet-Rich Plasma Versus Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis: Results at 5 Years of a Double-Blind, Randomized Controlled Trial. | journal=Am J Sports Med | year= 2019 | volume= 47 | issue= 2 | pages= 347-354 | pmid=30545242 | doi=10.1177/0363546518814532 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30545242 }} </ref> | ||
=== | === ''Complications'' === | ||
* The U.S. Food and Drug Administration recommends not to use more than 4,000 mg of acetaminophen/day in order to avoid its liver toxicity. | |||
* NSAIDs could cause adverse effects such as gastrointestinal bleeding, renal dysfunction, and blood pressure elevation. | |||
* Steroids injection has complications like breaking down the tissues, such as articular cartilage in the joint. Due to the important role of cartilage in joint system, most doctors refuse to use frequent cortisone injections in the same joint in a short period of time. | |||
==References== | ==References== |
Latest revision as of 07:46, 23 May 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammadmain Rezazadehsaatlou[2], Irfan Dotani [3].
Overview
As all diseases, the prevention and the early diagnosis and onetime treatment of OA play important roles patient final outcome. The treatment of OA can be categorized into two options. Treatment options of OA are: Nonsurgical (non-pharmacological, pharmacological, and complementary) and surgical interventions. As it always was, is, and will be, the patients have this right to get the best, safest, and least invasive therapies as their first treatment options. Meanwhile, surgical interventions should be considered in patients who have responded to the first line non/less invasive therapies inadequately. Meanwhile, the non-surgical treatments are often effective enough as the first line in patients management. Actually, the osteoarthritis treatment is a combination of medical therapies.
Medical Therapy
Non-pharmacological
Nonpharmacologic therapy is consisted of physical therapy and specific type of physical exercises, bracing and splinting:[1][2][3]
- Physical therapy results in short-term pain reduction, and improvement in physical function in the diseased joint to preserve its the ability for daily tasks like walking, dressing, and even bathing.
- Walking can reduce pain from osteoarthritis. A 1997 randomized controlled trial found 1 hour of walking based aerobic activity three times per week showed, over 18 months that older people with symptomatic osteoarthritis had consistent modest improvement in self-reported pain and disability compared with participation in health education programs. Futhermore, there seemed to be some correlation between increased amount of exercise and greater improvements in pain[4].
- On the other hand, resting is another important healing factor in OA.
- Bracing and splinting as other methods help to support painful or unstable joints.
- Using a cane can help decrease the weight pressure in diseased hip or knee, but it should be used on the contralateral side of the affected joint.
Analgesics
Drug therapy in OA management plays an important role in relieving pain and slow downing the progression of this disease. Meanwhile, common medications are:[5][6][7]
- NSAIDs (Non-steroidal anti-inflammatory drugs): Including acetaminophen, aspirin, ibuprofen (e.g. Advil), naproxen (e.g. Aleve), diclofenac, cyclooxygenase-2 inhibitors (celecoxib-Celebrex) are used to reduce the inflammation and swelling as a common finding in OA.
- Meanwhile, the glucosamine and chondroitin sulfate supplements are used in the United States as an alternative treatment for OA. For patients experiencing moderate-to-severe pain due to the knees osteoarthritis or spine osteoarthritis, they might be helpful by interacting with the diseased cartilage.
- Analgesics: Including acetaminophen (e.g. Tylenol), or tramadol (e.g. Ultram) are used to reduce the pain, without any effects on inflammation or swelling. Analgesics are recommended for patients experiencing mild to moderate pain because they could cause a limited variety of side effects for patients.
- Topical analgesics: These creams are usually used to reduce the pain in the diseased joint. They applied directly to the skin over the affected area. These creams consist of counterirritants (wintergreen and eucalyptus) which have a great effect on pain reduction. Capsaicin cream is derived from chili peppers and found to be effective in treating osteoarthritis pain, which can be applied as an adjunct therapy to the OA standard treatments. This group of therapies compared to NSAIDs had fewer adverse effects.
Medication | Typical dosage |
---|---|
Acetaminophen | 650 to 1,000 mg four times per day |
Celecoxib (Celebrex) | 200 mg per day |
Diclofenac sodium | 50 mg two to three times per day |
Diclofenac/misoprostol (Arthrotec) | 50 mg/200 mcg two to three times per day |
Ibuprofen, over-the-counter | 400 to 600 mg three times per day |
Meloxicam (Mobic) | 7.5 to 15 mg per day |
Nabumetone | 500 mg two times per day |
Naproxen, over-the-counter (Aleve) | 220 to 440 mg two times per day |
Naproxen (Naprosyn) | 250 to 500 mg two times per day |
Oxaprozin (Daypro) | 1,200 mg per day |
Sulindac (Clinoril) | 150 to 200 mg two times per day |
Corticosteroids
Cortisone are a group of man-made steroids simulating the cortisol effects in body. Cortisone injections are used for two most important reasons:
- I: Treatment option
- II: Diagnostic option
I: Treatment
Steroids (corticosteroid) have been used by injecting into the joint and reduce the inflammation, swelling, and pain in the diseased joint, for 6 weeks and 6 months period. However, studies report:
II: Diagnostic
In cases having an uncertain pain especially in hip and shoulder joints, the cortisone could be helpful in reaching accurate diagnoses. For example, if after the injection the patient's hip pain decreases, this means the pain originates from the hip. However, if the hip pain persisted after injection then other problems originating from the spine or the sacroiliac joint (the spine and pelvis) could be considered as the pain sources.
Platelet rich plasma
A meta-analysis of 6 randomized controlled trials and 4 non-randomized studies through June, 2014 found benefit for osteoarthritis of the knee[10]. The meta-analysis concluded only one trial[11] was not with high bias; however this trial does not report being registered.
A more recent meta-analysis of five randomized controlled trials published through December, 2019 found benefit compared to hyaluronic acid[12]. It is not clear that any of the trials were prospectively registered.
A more recent trial, that was registered after completion, but before long term follow-up was undertaken, found no benefit compared to hyaluronic acid[13]
Complications
- The U.S. Food and Drug Administration recommends not to use more than 4,000 mg of acetaminophen/day in order to avoid its liver toxicity.
- NSAIDs could cause adverse effects such as gastrointestinal bleeding, renal dysfunction, and blood pressure elevation.
- Steroids injection has complications like breaking down the tissues, such as articular cartilage in the joint. Due to the important role of cartilage in joint system, most doctors refuse to use frequent cortisone injections in the same joint in a short period of time.
References
- ↑ Lauche R, Cramer H, Langhorst J, Dobos G (January 2014). "A systematic review and meta-analysis of medical leech therapy for osteoarthritis of the knee". Clin J Pain. 30 (1): 63–72. doi:10.1097/AJP.0b013e31828440ce. PMID 23446069.
- ↑ Lauche R, Langhorst J, Dobos G, Cramer H (August 2013). "A systematic review and meta-analysis of Tai Chi for osteoarthritis of the knee". Complement Ther Med. 21 (4): 396–406. doi:10.1016/j.ctim.2013.06.001. PMID 23876571.
- ↑ Zhang Y, Huang L, Su Y, Zhan Z, Li Y, Lai X (2017). "The Effects of Traditional Chinese Exercise in Treating Knee Osteoarthritis: A Systematic Review and Meta-Analysis". PLoS ONE. 12 (1): e0170237. doi:10.1371/journal.pone.0170237. PMC 5266306. PMID 28121996.
- ↑ Ettinger WH, Burns R, Messier SP, Applegate W, Rejeski WJ, Morgan T; et al. (1997). "A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis. The Fitness Arthritis and Seniors Trial (FAST)". JAMA. 277 (1): 25–31. PMID 8980206.
- ↑ Watson M, Brookes ST, Faulkner A, Kirwan J (July 2007). "WITHDRAWN: Non-aspirin, non-steroidal anti-inflammatory drugs for treating osteoarthritis of the knee". Cochrane Database Syst Rev (1): CD000142. doi:10.1002/14651858.CD000142.pub2. PMID 17636601.
- ↑ Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, Hochberg MC, Wells G (April 2005). "Glucosamine therapy for treating osteoarthritis". Cochrane Database Syst Rev (2): CD002946. doi:10.1002/14651858.CD002946.pub2. PMID 15846645.
- ↑ Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G (January 2006). "Acetaminophen for osteoarthritis". Cochrane Database Syst Rev (1): CD004257. doi:10.1002/14651858.CD004257.pub2. PMID 16437479.
- ↑ McAlindon TE, LaValley MP, Harvey WF, Price LL, Driban JB, Zhang M; et al. (2017). "Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial". JAMA. 317 (19): 1967–1975. doi:10.1001/jama.2017.5283. PMC 5815012. PMID 28510679. Review in: Ann Intern Med. 2017 Sep 19;167(6):JC27
- ↑ Rhon DI, Boyles RB, Cleland JA (2014). "One-year outcome of subacromial corticosteroid injection compared with manual physical therapy for the management of the unilateral shoulder impingement syndrome: a pragmatic randomized trial". Ann Intern Med. 161 (3): 161–9. doi:10.7326/M13-2199. PMID 25089860. Review in: Evid Based Med. 2015 Apr;20(2):67
- ↑ Laudy AB, Bakker EW, Rekers M, Moen MH (2015). "Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis". Br J Sports Med. 49 (10): 657–72. doi:10.1136/bjsports-2014-094036. PMID 25416198.
- ↑ Sánchez M, Fiz N, Azofra J, Usabiaga J, Aduriz Recalde E, Garcia Gutierrez A; et al. (2012). "A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis". Arthroscopy. 28 (8): 1070–8. doi:10.1016/j.arthro.2012.05.011. PMID 22840987.
- ↑ Zhao J, Huang H, Liang G, Zeng LF, Yang W, Liu J (2020). "Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis". BMC Musculoskelet Disord. 21 (1): 224. doi:10.1186/s12891-020-03262-w. PMC 7149899 Check
|pmc=
value (help). PMID 32278352 Check|pmid=
value (help). - ↑ Di Martino A, Di Matteo B, Papio T, Tentoni F, Selleri F, Cenacchi A; et al. (2019). "Platelet-Rich Plasma Versus Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis: Results at 5 Years of a Double-Blind, Randomized Controlled Trial". Am J Sports Med. 47 (2): 347–354. doi:10.1177/0363546518814532. PMID 30545242.