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Are intra-articular injections in the treatment of knee osteoarthritis effective enough?

Authors:
O. Sahap Atik
O. Sahap Atik
Laszlo Hangody at Uzsoki Hospital and Semmelweis University
Laszlo Hangody
  • Uzsoki Hospital and Semmelweis University
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Joint Diseases and
Related Surgery
Jt Dis Relat Surg
2022;33(3):487-488
EDITORIAL
Are intra-articular injections in the treatment of
knee osteoarthritis effective enough?
O. Şahap Atik, MD1, Laszlo Rudolf Hangody, MD, PhD2
1President, Turkish Joint Diseases Foundation, Ankara, Türkiye
2Department of Orthopedics and Trauma, Uzsoki Hospital, Budapest, Hungary
outcomes in patients with knee OA at up to
one-year follow-up.
Osteochondral lesions are frequently observed
and caused by an acute or repetitive traumatic
event. The damage of articular cartilage can cause
pain, effusion, OA, and joint dysfunction.[3] A study
evaluated the effect of adipose-derived SVF on
osteochondral defects treated by a combination of
microfractures (MFs) and HA-based scaffold in a
rabbit model.[3] The authors concluded that it could
be used to accelerate cartilage regeneration, thus, in
the treatment of secondary OS.
A total of 43 trials involving 5,554 patients were
included in another meta-analysis.[4] The authors
reported that IA injections of HA or CS were
associated with better outcomes than PRP, adipose
MSC or placebo in knee OA. Single PRP, multiple
PRP, and adipose MSC interventions did not result
in a relevant reduction of joint pain nor improvement
of joint function compared to placebo. For pain relief
and adverse effects, steroids are most likely the most
optimal treatment followed by HA.
There is overwhelming information about PRP,
BMAC, and MSC, but there are less evidence-based
support than media promotions and highlights
currently. Low-dose IA steroids for synovitis and
high-molecular weight HA injections for dry
osteoarthritic knees have more reliable literature
support than new orthobiologics.[5]
In an editorial, Bannuru[6] commented that
“Intra-articular corticosteroids are useful for acute and
short-term pain relief, whereas hyaluronic acid is useful
for a longer-term treatment effect for patients with knee
osteoarthritis. More rigorous research using homogeneous
preparations and techniques and randomizing larger
numbers of knee osteoarthritis patients are warranted before
Received: August 26, 20 22
Accepted: Au gust 26, 2 022
Published online: Octobe r 06, 2022
Correspondence: O. Şahap Ati k, MD. Turki sh Joi nt Dise ases
Found ation, M ustafa Kemal Mah., Dumlu pınar Bul., 274/2,
C2 Blok, Ofis 5, 0 690 0 Çankaya, Ankara, Türkiye.
E-mail: satikmd@gmail.com
Doi: 10.52312/jd rs.2022. 57907
Citation: Atik OŞ, Hangody LR. Are int ra-a rticular injection s in the
treatment of knee osteoarthritis effective enough?. Jt Dis Relat
Surg 2022;33(3):487-488.
This is an open access article under the terms of the Creative
Commons Attribution-NonCommercial License, which permits use,
distribution and reproduction in any medium, provided the original
work is properly cited and is not used for commercial purposes
(http://creativecommons.org/licenses/by-nc/4.0/).
©2022 All right reserved by the Turkish Joint Diseases Foundation
The use of intra-articular injections (IAs) in the
treatment of osteoarthritis (OA) has gained wide
popularity in recent years. The relatively low cost,
rapid and simple method of pain relief are its main
advantages.[1] However, most articles have reported
insufficient sample size with a varying follow-up
period which results in difficulty in formulating and
implementing clinical recommendations.
Seventy-nine randomized controlled trials
(RCTs) with 8,761 patients were included in a
meta-analysis.[2] Intra-articular injections evaluated
included autologous conditioned serum (ACS), bone
marrow aspirate concentrate (BMAC), botulinum
toxin, corticosteroids (CSs), hyaluronic acid (HA),
mesenchymal stem cells (MSCs), ozone, saline
placebo, platelet-rich plasma (PRP), plasma rich
in growth factor (PRGF), and stromal vascular
fraction (SVF). The authors concluded that current
evidence indicated that SVF injections resulted in
the greatest improvement in pain and functional
Jt Dis Relat Surg488
recommending any wider acceptance of platelet-rich plasma
and stem cell therapies. This is of utmost importance,
especially with several new injectables such as anti-nerve
growth factor antibodies, Wnt pathway inhibitors, and
capsaicin showing promise to enter the market soon.”
Current clinical experience on orthobiologics
should be regarded as the first steps for the new
concept of musculoskeletal system healing and is
still in experimental stage. No definitive conclusions
can be established about the effects of PRP in such
conditions, since most studies are of low-to-moderate
methodological quality and use variable PRP
protocols.[7]
In conclusion, the true extent of the benefits of IA
injections is still being debated. Intra-articular CSs
should not be administered frequently. Biological
agents including MSC, BMAC, and PRP may have a
great potential, but unrestricted utilization cannot be
recommended, as high-quality scientific evidence is
still lacking in the modern literature.
REFERENCES
1. Rampal S, Jaima n A, Tokgöz MA, Ar umugam G, Sivanant han
S, Singh RSJ, et al. A review of the efficacy of intraarticular
hip injection for patients with hip osteoarthritis: To inject
or not to inject in hip osteoarthritis? Jt Dis Relat Surg
2022;33:255-62.
2. Anil U, Markus DH, Hurley ET, Manjunath AK, Alaia
MJ, Campbell KA, et al. The efficacy of intra-articular
injections in the treatment of knee osteoarthritis: A
network meta-analysis of randomized controlled trials.
Knee 2021;32:173-82.
3. Şahin AA,Değirmenci E, Özturan KE, Fırat T,Kükner A.
Effects of adipose tissue-derived stromal vascular fraction
on osteochondral defects treated by hyaluronic acid-
based scaffold: An experimental study. Jt Dis Relat Surg
2021;32:347-54.
4. Han SB, Seo IW, Shin YS. Intra-articular injections of
hyaluronic acid or steroids associated with better outcomes
than platelet-rich plasma, adipose mesenchymal stromal
cells, or placebo in knee osteoarthritis: A network meta-
analysis. Arthroscopy 2021;37:292-306.
5. Hangody L, Szody R, Lukasik P, Zgadzaj W, Lénárt E,
Dokoupilova E, et al. Intraarticular injection of a cross-
linked sodium hyaluronate combined with triamcinolone
hexacetonide (Cingal) to provide symptomatic relief of
osteoarthritis of the knee: A randomized, double-blind,
placebo-controlled multicenter clinical trial. Cartilage
2018;9:276-83.
6. Bannuru RR. Editorial commentary: Intra-articular
injections for painful knee osteoarthritis: What is the
current treatment paradigm? Arthroscopy 2021;37:307-8.
7. Atik OŞ. Do patients benefit from platelet-rich plasma?
Jt Dis Relat Surg 2020;31:409-10.
... Knee osteoarthritis (OA) is a condition characterized by significant pain resulting from the gradual deterioration of joint cartilage. [1,2] The incidence of OA has been rapidly increasing due to the aging population. Managing OA presents a formidable therapeutic challenge due to its intricate pathophysiology and limited effective treatments. ...
... Despite the array of therapeutic options available, the current lineup primarily focuses on alleviating clinical symptoms rather than addressing the underlying disease causes. [2,3] For mild cases of OA, approaches such as patient education, pain management, and lifestyle adjustments are commonly employed. These include incorporating physical therapy and rehabilitation techniques. ...
... These While intra-articular injection therapies form a cornerstone of nonsurgical approaches for OA patients, there exists controversy regarding the optimal injectable treatment for such individuals. [2] Hyaluronic acid (HA) injections present an alternative option for treating OA by replenishing synovial fluid and restoring joint viscoelasticity. [6,7] Several studies have demonstrated the benefits of HA for OA patients, [6,8] and this widely distributed glycosaminoglycan is naturally found in human cartilage, synovial fluid, and membranes. ...
Effectiveness of gonarthrosis treatment via intra-articular injections of linear vs. cross-linked hyaluronic acids
Article
Full-text available
  • Nov 2023
Objectives The study aimed to compare the outcomes of single-dose cross-linked hyaluronic acid and the linear regimen of three doses of HA knee injections among patients with gonarthrosis. Patients and methods This single-center, retrospective study was conducted with 60 patients (47 females, 13 males; mean age: 57.9±4.29 years; range, 50 to 65 years) with Kellgren-Lawrence Grade 2 or 3 gonarthrosis between February 2020 and February 2022. Patients were either subjected to intra-articular cross-linked hyaluronic acid (n=30) or linear hyaluronic acid (n=30) injection treatments. Comprehensive assessments of the patients were conducted prior to the injections, as well as at three and six months after injection. The two injection groups were compared regarding the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Oxford Knee Score. Results Both injections showed a statistically significant improvement from baseline in both WOMAC and Oxford Knee Score at three and six months (p<0.001). There was no notable distinction in the alteration of WOMAC knee scores between the two injection types. However, a notable discrepancy was observed in the elevation of Oxford Knee Score among patients who received cross-linked knee injections compared to those who underwent linear hyaluronic acid knee injections, signifying a significant increase in the former group (p<0.001). Conclusion The advantage of a single-dose administration of cross-linked HA knee injections, as opposed to the three-dose regimen required for linear hyaluronic acid, translates into reduced time and cost for the injection process. Moreover, this approach minimizes injection-associated discomfort for patients due to the singular dose administration.
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... [3] Intra-articular injections are relatively less invasive procedures, and materials such as hyaluronic acid (HA), platelet-rich plasma, and corticosteroids can be administered. [4] It has been reported that HA-based scaffolds and adipose tissue-derived stromal vascular fraction treatment increased hyaline cartilage formation and cartilage thickness in osteochondral defects in a rabbit model. [5] Lactoferrin (LF) is an 80 kDa non-heme iron-binding glycoprotein that belongs to the transferrin family [6] and, recently, its proliferative and anti-apoptotic properties have been shown. ...
View
... Being a non-sulfated glycosaminoglycan with a low antigenic structure with excellent compatibility, HA is involved in the structure of cartilage in joints and in the composition of articular synovial fluid. [15] The American College of Rheumatology (ACR) and The European Alliance of Associations for Rheumatology (EULAR) guidelines for the management of patients with OA also recommend the use of HA. [16,17] The NAC group showed more improvement than the control group. This result made NAC treatment researchable, applicable, and promising in cartilage healing. ...
In vivo study of the role of hyaluronic acid, N-acetyl cysteine, and deproteinized calf serum on injury-induced cartilage degeneration
Article
Full-text available
  • Dec 2022
Objectives: The aim of this study was to compare the effects of hyaluronic acid (HA), N-acetyl cysteine (NAC), and deproteinized calf serum on cartilage healing after the creation of traumatic cartilage injury in a rat model. Materials and methods: A total of 48 rats, each weighing an average of 350 g, were randomly separated into four groups of 12. An osteochondral defect was created, 2-mm-wide and 3-mm deep in each rat. Injections were made to the knees of the rats as saline solution in Group 1, deproteinized calf serum in Group 2, NAC in Group 3, and HA in Group 4. At the end of 12 weeks, all rats were sacrificed and tissues were evaluated histologically. Results: The HA group had a better cell morphology, tissue morphology, surface architecture, and vascularity than the other groups (p<0.001). Matrix staining, chondrocyte clustering, and the assessment scores of the mid, deep, superficial zones, and overall were higher in the HA group than in the other groups (p<0.001). The NAC showed a better tissue morphology, cell morphology, and vascularity than the control group (p=0.003, p<0.001, and p<0.001, respectively). Conclusion: Hyaluronic acid was the most effective agent in cartilage healing compared to NAC and deproteinized calf serum. In addition, the NAC was more effective compared to the control group.
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... The relatively low cost, rapid and simple method of pain relief are its main advantages. [1] However, the majority of the articles have reported insufficient sample size with a varying follow-up period, resulting in difficulty in formulating and implementing clinical recommendations. Therefore, the true extent of the benefits of IA injections is still being debated. ...
View
... [3] Thus, intra-articular HA has a significant effect on the pain and function improvement of OA and is recommended for the management of OA in knee, hip, and other joints. [4,5] Intra-articular HA injection is a safe alternative therapeutic option for TMC OA and has been widely clinically applied. However, recent meta-analysis and systemic reviews have revealed the scientific evidence on the efficacy of intra-articular HA in TMC OA as equivocal and inconclusive due to the great heterogeneity of clinical trials, and many of its effects have not been investigated clinically. ...
Comparison of intra-articular injection of ArtiAid®-Mini with Ostenil®-Mini for trapeziometacarpal osteoarthritis: A double-blind, prospective, randomized, non-inferiority trial
Article
Full-text available
  • Jan 2023
Objectives: This study aims to compare the effectiveness and safety of intra-articular hyaluronic acid (HA) injections of ArtiAid®-Mini (AAM) and Ostenil®-Mini (OM) for the treatment of trapeziometacarpal joint osteoarthritis. Patients and methods: Between February 2018 and April 2020, this 24-week, double-blind, prospective, randomized, non-inferiority trial included a total of 17 patients (8 males, 9 females; mean age: 60.3±9.5 years; range, 42 to 76 years) who were treated with either intra-articular AAM (n=8) or OM (n=9). The primary outcome was pain according to a change in Visual Analog Scale (VAS) at 12 weeks after the last injection. The secondary outcomes included the change of VAS at Weeks 2, 4, and 24 after the injection, satisfaction, range of motion (ROM) of trapeziometacarpal joint, pinch strength, grip strength, and adverse events at Weeks 2, 4, 12, and 24 after the injection. Results: Eight patients with AAM and eight patients with OM completed the follow-up. No significant differences in primary and secondary outcomes were observed between the two groups at baseline and each time point (p>0.05). The intra-group differences were significant in each time point. Conclusion: The intra-articular injection of either AAM or OM is effective and safe for patients with trapeziometacarpal osteoarthritis up to 24 weeks.
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... [3] Intra-articular injections are relatively less invasive procedures, and materials such as hyaluronic acid (HA), platelet-rich plasma, and corticosteroids can be administered. [4] It has been reported that HA-based scaffolds and adipose tissue-derived stromal vascular fraction treatment increased hyaline cartilage formation and cartilage thickness in osteochondral defects in a rabbit model. [5] Lactoferrin (LF) is an 80 kDa non-heme iron-binding glycoprotein that belongs to the transferrin family [6] and, recently, its proliferative and anti-apoptotic properties have been shown. ...
Comparison of the efficacy of intra-articular injections of hyaluronic acid and lactoferrin in mono-iodoacetateinduced temporomandibular joint osteoarthritis: A histomorphometric, immunohistochemistry, and micro-computed tomography analysis
Article
Full-text available
  • Jan 2023
Objectives: This study aims to evaluate the efficacy of high-molecular-weight hyaluronic acid (HMWHA) and lactoferrin (LF) injections on temporomandibular joint (TMJ) cartilage and subchondral bone in mono-iodoacetate (MIA)-induced temporomandibular joint osteoarthritis model in rats. Materials and methods: In this in vivo study, a total of 24 rats were divided into three groups as follows: saline group (Group 1), HMWHA group (Group 2), and LF group (Group 3) including eight rats in each group. The intra-articular injections were administered once a week for three weeks after osteoarthritis was induced. All animals were euthanized 28 days after induction of osteoarthritis, and TMJs were harvested for histomorphometric, immunohistochemical, and micro-computed tomography (CT) analysis. Results: There was no significant difference between the HMWHA and LF groups in terms of the histomorphometric and immunohistochemical analysis results (p>0.05). According to the micro-CT analysis, the LF group had the highest mean bone volume fraction (74.9±0.5) and trabecular thickness (0.122±0.002), while the saline group had the lowest mean values (55.0±0.3 and 0.071±0.002, respectively) (p<0.001). There was no significant difference between the HMWHA and LF groups according to the micro-CT analysis (p>0.05). Both groups had better healing effects than the saline group in all analyses. Conclusion: Lactoferrin has a healing effect at least as much as HMWHA in MIA-induced TMJ osteoarthritis. We suggest that LF may be evaluated in future clinical studies as a promising agent in the treatment of osteoarthritis.
View
A review of the efficacy of intraarticular hip injection for patients with hip osteoarthritis: To inject or not to inject in hip osteoarthritis?
Article
Full-text available
  • Mar 2022
Hip injection (HI) for osteoarthritis (OA) are in vogue nowadays. Corticosteroids (CSs) and hyaluronic acid (HA) gel are the two most common agents injected into the hip. Off late, platelet-rich plasma (PRP), mesenchymal stem cell (MSC), bone marrow aspirate concentrate (BMAC), local anesthetic (LA) agents, non-steroidal anti-inflammatory drugs (NSAIDs) and their different combinations have also been injected in hips to provide desired pain relief. However, there is a group of clinicians who vary of these injections. A search of the literature was performed on PubMed, Cochrane Library, and DOAJ using the keywords "hip osteoarthritis injection". Data were analyzed and compiled. Intraarticular CSs are effective in providing the desired pain relief in OA hip, but repeated injections should be avoided and the interval between HI and hip arthroplasty must be kept for more than three months. Methylprednisolone or triamcinolone are combined with 1% lidocaine or 0.5% bupivacaine. Chondrotoxic effects of LA is a concern. Although national guidelines do not favor the use of HA for hip OA, numerous publications have favored its usage for a moderate grade of OA. The PRP, MSC, and BMAC are treatment options with great potential; however, currently, the evidence is conflicting on their role in hip OA. There is always a risk of septic arthritis, particularly when aseptic precautions are not followed, and clinicians must vary of this complication.
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Effects of Adipose Tissue-Derived Stromal Vascular Fraction on Osteochondral Defects Treated by Hyaluronic Acid-Based Scaffold: An Experimental Study
Article
Full-text available
  • Jun 2021
Objectives: This study aims to evaluate the effect of adipose-derived stromal vascular fraction (SVF) on osteochondral defects treated by hyaluronic acid (HA)-based scaffold in a rabbit model. Materials and methods: Eighteen white New Zealand rabbits were randomly grouped into the experimental group (n=9) and control group (n=9). In all groups, osteochondral defects were induced on the weight-bearing surfaces of the right femoral medial condyles, and a HA-based scaffold was applied to the defect area with microfractures (MFs). In this study, 1 mL of adipose-derived SVF was injected into the knee joints of the rabbits in the experimental group. For histological and macroscopic evaluation, four rabbits were randomly selected from each group at Week 4, and the remaining rabbits were sacrificed at the end of Week 8. Macroscopic assessments of all samples were performed based on the Brittberg scoring system, and microscopic evaluations were performed based on the O'Driscoll scores. Results: Samples were taken at Weeks 4 and 8. At Week 4, the O'Driscoll scores were significantly higher in the control group than the experimental group (p=0.038), while there was no significant difference in the Brittberg scores between the two groups (p=0.108). At Week 8, the O'Driscoll score and Brittberg scores were statistically higher in the experimental group than in the control group (p=0.008 and p=0.007, respectively). According to the microscopic evaluation, at the end of Week 8, the cartilage thickness was greater in the experimental group, and nearly all of the defect area was filled with hyaline cartilage. Conclusion: Application of adipose-derived SVF with MF-HA-based scaffold was better than MF-HA-based scaffold treatment in improving osteochondral regeneration. Therefore, it can be used in combination with microfracture and scaffold to accelerate cartilage regeneration, particularly in the treatment of secondary osteoarthritis.
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Intraarticular Injection of a Cross-Linked Sodium Hyaluronate Combined with Triamcinolone Hexacetonide (Cingal) to Provide Symptomatic Relief of Osteoarthritis of the Knee: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Trial
Article
Full-text available
Objective: To evaluate the efficacy and safety of an intraarticular injection of Cingal (Anika Therapeutics, Inc., Bedford, MA) compared with Monovisc (Anika Therapeutics, Inc., Bedford, MA) or saline for the treatment of knee osteoarthritis. Design: This multicenter, double-blind, saline-controlled clinical trial randomized subjects with knee osteoarthritis (Kellgren-Lawrence grades I-III) to a single injection of Cingal (4 mL, 88 mg hyaluronic acid [HA] plus 18 mg triamcinolone hexacetonide [TH]), Monovisc (4 mL, 88 mg HA), or saline (4 mL, 0.9%). The primary efficacy outcome was change in WOMAC (Western Ontario and McMaster Universities Arthritis Index) Pain Score through 12 weeks with Cingal versus saline. Secondary outcomes included Patient and Evaluator Global Assessments, OMERACT-OARSI Responder index, and WOMAC Total, Stiffness, and Physical Function scores through 26 weeks. Results: A total of 368 patients were treated (Cingal, n = 149; Monovisc, n = 150; saline, n = 69). Cingal improvement from baseline was significantly greater than saline through 12 weeks ( P = 0.0099) and 26 weeks ( P = 0.0072). WOMAC Pain was reduced by 70% at 12 weeks and by 72% at 26 weeks with Cingal. Significant improvements were found in most secondary endpoints for pain and function at most time points through 26 weeks. At 1 and 3 weeks, Cingal was significantly better than Monovisc for most endpoints; Cingal and Monovisc were similar from 6 weeks through 26 weeks. A low incidence of related adverse events was reported. Conclusions: Cingal provides immediate and long-term relief of osteoarthritis-related pain, stiffness, and function, significant through 26 weeks compared to saline. Cingal had similar immediate advantages compared with HA alone, while showing benefit comparable to HA at 6 weeks and beyond.
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The efficacy of intra-articular injections in the treatment of knee osteoarthritis: A network meta-analysis of randomized controlled trials
Article
  • Oct 2021
  • KNEE
Purpose Osteoarthritis (OA) is a debilitating joint disease characterized by progressive loss of articular cartilage. Intra-articular injections are a mainstay of nonoperative treatment, however, there is controversy as to the optimal injectable for these patients. The purpose of the current study is to perform a network meta-analysis of the randomized control trials in the literature to ascertain whether there is a superior injectable nonoperative treatment for knee OA. Methods The literature search was conducted based on the PRISMA guidelines. Randomized control trials (RCTs) evaluating intra-articular injectables in osteoarthritic knees were included. Data was extracted and Visual Analogue Scale (VAS) scores and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, where available were analyzed at 1, 3, 6 and 12 months. Clinical outcomes were compared using a frequentist approach to network meta-analysis, with statistical analysis performed using R. The treatment options were ranked using the P-Score. Results Seventy-nine RCTs with 8761 patients were included in this review. Intra-articular injectables evaluated included autologous conditioned serum (ACS), bone marrow aspirate concentrate (BMAC), botulinum toxin, corticosteroids (CS), hyaluronic acid (HA), mesenchymal stem cells (MSC), ozone, saline placebo, platelet-rich plasma (PRP), plasma rich in growth factor (PRGF), and stromal vascular fraction (SVF). At 4–6 weeks and 3 months of follow-up, the treatment with the highest P-Score for WOMAC score was high molecular weight (HMW) HA + CS [P-Score = 0.9500 and 8503, respectively]. At 6-months follow-up, the treatment with the highest P-Score for WOMAC score was PRP [P-Score = 0.7676]. At all post-injection time points, the treatment with the highest P-Score for VAS score [P-Score Range = 0.8631–9927] and Womac score at 12 Months [P-Score = 0.9044] was SVF. Conclusions The current evidence shows that SVF injections result in the greatest improvement in pain and functional outcomes in patients with knee OA at up to 1 year of follow-up.
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Intra-articular injections for painful knee osteoarthritis - what is the current treatment paradigm
Article
  • Sep 2020
  • ARTHROSCOPY
Intra-articular corticosteroids are useful for acute and short-term pain relief, whereas hyaluronic acid is useful for a longer-term treatment effect for patients with knee osteoarthritis. More rigorous research using homogenous preparations and techniques, randomizing larger numbers of knee osteoarthritis patients are warranted before recommending any wider acceptance of platelet-rich plasma and stem cell therapies. This is of utmost importance especially with several new injectables such as anti-nerve growth factor antibodies, Wnt pathway inhibitors and capsaicin showing promise to enter the market soon.
View
Intra-Articular Injections of Hyaluronic Acid or Steroids Associated With Better Outcomes Than Platelet-Rich Plasma, Adipose Mesenchymal Stromal Cells, or Placebo in Knee Osteoarthritis: A Network Meta-Analysis
Article
  • Apr 2020
Purpose This study aims to evaluate the clinical effects of hyaluronic acid (HA), steroid, platelet-rich plasma (PRP), or adipose mesenchymal stromal cell (MSC) injections in the treatment of knee osteoarthritis (OA). Materials and Method Randomized controlled trials (RCTs) with OA of the knee that compared HA, steroid, PRP, adipose MSC, or their combination with placebo or in head-to-head combination were identified from the MEDLINE, EMBASE, Cochrane Library, Web of Science, and SCOPUS databases up toJune30, 2019. We performed a network meta-analysis (NMA) of the relevant literature to determine if there is benefit from HA, steroid, PRP, or adipose MSC treatment as compared with placebo. Results A total of 43 trials covering 5,554 patients were included. Steroid was ranked most likely to be effective for the management of pain or function, with adipose MSC and multiple PRP appearing least likely to be effective. Although no significant difference was observed among the six interventions, except for single PRP with respect to adverse effects (AEs), steroid and HA exhibited a lower rate of AEs compared with the placebo. In view of severe adverse effects (SAEs), only single PRP was superior to placebo. Direct pairwise meta-analysis for pain relief showed that HA was superior to placebo or single PRP, but steroid had a significantly worse effect than single PRP. In addition, direct pairwise meta-analysis for AEs favored steroid in comparison to HA. Conclusion The ranking statistics like surface under the cumulative ranking curve values of our NMA support the use of steroid and HA for appropriate patients with knee OA. For pain relief and AEs, steroid is most likely the best treatment, followed by HA. Single PRP, multiple PRP, and adipose MSC interventions do not result in a relevant reduction of joint pain nor improvement of joint function compared with placebo. However, treatment effect differences were small and potentially not clinically meaningful, indicating that other factors, such as cost and patient preferences, may be more important in patients with knee OA.
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Editorial commentary: Intra-articular injections for painful knee osteoarthritis: What is the current treatment paradigm
  • Jan 2021
  • 307-308
  • RR Bannuru
Bannuru RR. Editorial commentary: Intra-articular injections for painful knee osteoarthritis: What is the current treatment paradigm? Arthroscopy 2021;37:307-8.