Exercise for Osteoarthritis of the Knee a Cochrane Systematic Review

• Journal Listing
• J Int Med Res
• v.48(four); 2020 Apr
• PMC7783274

J Int Med Res. 2020 Apr; 48(iv): 0300060519895868.

The efficacy and safety of Botulinum Toxin Blazon A in painful knee osteoarthritis: a systematic review and meta-analysis

Shuchao Zhai

^aneDepartment of Orthopedics, Tianjin Fifth Central Infirmary Tianjin, Communist china

Botao Huang

²Department of Orthopedics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, Red china

Kai Yu

ⁱSection of Orthopedics, Tianjin Fifth Central Hospital Tianjin, Cathay

Received 2019 Aug one; Accepted 2019 Nov 28.

Abstract

Objective

A systematic review and meta-analysis was carried out to evaluate the efficacy and prophylactic of Botulinum Toxin Type A in painful knee osteoarthritis.

Methods

The EMBASE and MEDLINE databases were searched to identify randomized controlled trials (RCTs) of Botulinum Toxin Type A in the handling of painful knee osteoarthritis. The references of included literature were likewise searched.

Results

Five articles involving 5 RCTs including 314 patients were included in this analysis. At that place was a significant departure betwixt Botulinum Toxin Blazon A and placebo in the visual analog calibration (VAS) pain calibration and Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) questionnaire score in both the curt-term (≤iv weeks) and long-term (≥8 weeks) treatment period. At that place were no serious adverse events in the Botulinum Toxin Type A groups.

Conclusions

This meta-analysis suggests that Botulinum Toxin Type A is effective and safe in the painful knee joint OA treatment. However, loftier-quality randomized controlled studies are still needed to further confirm our findings.

Keywords: Botulinum Toxin Blazon A, human knee osteoarthritis, genu hurting, randomized controlled trial, systematic review, meta-analysis

Introduction

Osteoarthritis (OA) is one of the nearly common forms of arthritis in patients, and is a common blazon of joint affliction in the elderly. The knee is a common cause of chronic hurting.¹ Knee OA is a chronic and progressive disease that is one of the most common joint disorders around the earth.² It is characterized by articular cartilage degeneration, bony changes, and osteophyte germination. Knee OA often leads to swelling and joint pain and dysfunction, which may touch on patients' quality of life and contribute to depression.ⁱⁱⁱ

The primary aims in the handling of knee OA are relieving pain, reducing the inflammatory response, restoring part, and slowing the progression of the disease. The American Higher of Rheumatology has recommended an initial noninvasive and nonoperative treatment programme for knee OA that includes rest, weight loss, physical modalities, bracing and therapeutic exercises, assistive devices, and pharmacological interventions.^iv The about common pharmacological interventions include oral and topical analgesics, cyclooxygenase-2 inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids.^v Besides, if orally administered drugs cannot control symptoms, intraarticular (IA) injections can be a last nonoperative option. However, the therapeutic effect of IA injections is uncertain.⁶ Limited evidence has suggested that corticosteroids in knee OA therapy may exist effective, especially in controlling pain, but simply in the short term.⁷

Botulinum toxin type A (BoNT-A) has been used clinically for its paralytic effects, while increasing evidence suggests that it may have a role in hurting modulation. Two previous meta-analyses published in 2017 and 2018 indicated that compared with placebo, BoNT-A IA injections accept beneficial effects, with improved pain and WOMAC score in adult patients with refractory joint pain.^eight,nine Nonetheless, thus far no meta-analysis or systematic review has been performed that has focused on the efficacy and rubber of BoNT-A in painful knee OA.

The purpose of our study was to perform a systematic review and meta-analysis to evaluate the efficacy and safety of BoNT-A in treating painful knee OA.

Materials and methods

We searched Medline, Cochrane Controlled Trials Annals databases, and Embase for randomized controlled trials (RCTs) published earlier Jul 1, 2019 using the following search criteria: Botulinum Toxin Type A, genu osteoarthritis, and RCTs. We express our search to published studies in English only and obtained certain essential information directly from the authors for some studies. Besides, we screened the relevant references of included studies to identify other possible studies for inclusion.

Inclusion criteria

In our search, accustomed studies were to include the following characteristics: (ane) BoNT-A therapy and placebo therapy analyzed for patients with knee osteoarthritis; (two) full text bachelor; and (3) visual analog scale (VAS) pain calibration and Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) questionnaire score.

Quality assessment

We used the Jadad scale to assess the quality of individual studies.¹⁰ We evaluated the quality of the studies based on allocation sequence generation, blinding method, and concealment of the allotment process. We divided the quality of each study into three levels: quality degree "A" if the study satisfied all quality criteria; quality degree "B" if the written report had one or more ambiguous quality criteria; and quality degree "C" if the study had a loftier chance of bias and met few of the quality criteria. All of the authors assessed the quality of the RCTs and agreed with the concluding results.

Data extraction

We recorded the following data from the studies: (1) the authors' kickoff names and year of publication; (2) intervention method; (three) sample size; (4) inclusion criteria; (5) follow-upward time, and (6) changes in the VAS pain scale and WOMAC questionnaire score.

Statistical analysis and meta-analysis

We used the RevMan (Version v.three. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) to clarify differences betwixt the variables.¹¹ Using the included studies' data, nosotros summarized changes in VAS hurting scale and WOMAC questionnaire score. Nosotros used the hateful departure (MD) to evaluate the continuous data, and nosotros used the odds ratio (OR) with 95% confidence intervals (CI) to evaluate dichotomous data. A fixed-furnishings model was considered suitable for studies with p > 0.05, which was recognized equally homogeneous. Inconsistent results were analyzed using the I² statistic, which represents the proportion of heterogeneity among the studies. We used a random-effects model for studies with a p < 0.05 and where I² > 50%. We considered p < 0.05 to indicate statistical significance.¹²

Results

Characteristics of private studies

Our search identified 34 studies, and after reviewing their abstracts we excluded 15 studies. Among the remaining 19 studies, xiv studies were excluded for lack of useful data. Finally, 5 RCTs^{thirteen–17} were used to evaluate the efficacy and safety of BoNT-A in painful articulatio genus OA (Figure ane describes the search procedure in detail). Table 1 shows the baseline characteristics of these 5 studies.

A flow diagram of the study selection process. RCT, randomized controlled trial.

Tabular array ane.

Study and patient characteristics

Study	Therapy in experimental group	Therapy in control group	Land	Sample size		Administration method	Duration of handling	Dosage	Inclusion population
				Experimental	Command
Mahowald ML 2009	BoNT-A	Placebo	United states of america	21	21	Intraarticular injection	4/12 westward	100 U	Arthritis knee pain ≥4.5 NRS; had not responded adequately to oral analgesic medications or intra-articular injections of corticosteroids and/or viscosupplements.
Arenelt-Nielsen 50 2016	BoNT-A	Placebo	Denmark	61	lx	Intraarticular injection	4/8 w	200 U	Idiopathic knee OA who have had stable knee hurting for ≥ vi months before visit 1, with an ADWP score of four.0–ix.0.
Hsieh LF 2016	BoNT-A	Placebo	Taiwan	21	20	Intraarticular injection	one/18 west	100 U	Articulatio genus OA disease elapsing ≥ three months with a radiographic OA severity grade between two and three, VAS score ≥ 4, and failure of previous bourgeois treatments.
Bao X 2018	BoNT-A	Placebo	China	twenty	20	Intraarticular injection	4/8 w	100 U	Radiographic OA severity grade ≥two and hurting VAS score ≥6; failure of physical therapy and/or medical treatment in the last 3 months; involvement of unilateral human knee joint through clinical cheque and bilateral X-ray of the knees.
Mendes JG 2019	BoNT-A	Placebo	Brazil	35	35	Intraarticular injection	4/8 w	100 U	Mild to moderate OA according to the Kellgren-Lawrence classification (grades Two or 3), knee pain for more than six months, human knee pain at rest between three and eight cm.

Quality of the individual studies

All 5 of the included studies were RCTs. Each of the included studies had a scientific calculation of sample size. The intention-to-treat analysis was shown in one written report.¹⁷ All of the included studies were of high quality, with a Jadad scores rating A (Tabular array two). The plot was highly symmetrical and no evidence of bias was plant (Figure 2).

Table ii.

Quality assessment of private studies

Study	Resource allotment sequence generation	Allocation concealment	Blinding	Loss to follow-up	Calculation of sample size	Statistical analysis	Level of quality
Mahowald ML 2009	A	A	A	0	YES	Not mentioned	B
Arenelt-Nielsen L 2016	A	A	A	1	Yeah	Analysis of variance	A
Hsieh LF 2016	A	A	A	0	Aye	Mann-Whitney U test	A
Bao X 2018	A	A	A	0	YES	Analysis of variance	A
Mendes JG 2019	A	A	A	6	YES	Analysis of variance	A

Funnel plot of the studies represented in the meta-analysis.

MD: mean difference, SE: standard mistake.

Efficacy

Nosotros studied the changes in the measurement parameters in both the short-term (≤four weeks) and long-term (≥8 weeks) treatment menstruation to determine the efficacy of BoNT-A in painful knee OA.

VAS pain scale

Measurements at short-term (≤4 weeks)

Five studies involving 314 human knee OA patients (158 in the BoNT-A therapy group and 156 in the placebo group) contained meaningful data on VAS pain scale. A random-effects model was used to evaluate changes betwixt the two groups, which showed a MD of −1.21 (95% CI: −1.88 to −0.55, P=0.0004). Patients who received BoNT-A IA injection therapy had obvious comeback in the brusk-term VAS pain scale (Figure 3a).

Woods plots showing changes in (a) VAS hurting scale short-term (≤4 weeks) and (b) VAS pain calibration long-term (≥8 weeks) in the handling studies.

BoNT-A: Botulinum toxin type A, SD: standard difference, IV: changed variance, CI: conviction interval VAS: visual analog calibration.

Measurements at long-term (≥8 weeks)

Four studies enrolling 272 articulatio genus OA patients (137 in the BoNT-A IA injection therapy grouping and 135 in the placebo grouping) were included, and a random-furnishings model revealed a significant decrease in the long-term VAS pain scale (MD: −1.40, 95% CI: −2.21 to −0.60, P = 0.0006). (Effigy 3b).

WOMAC questionnaire score

Measurements at short-term (≤iv weeks)

Four studies including iv comparisons were used to clarify results for WOMAC questionnaire score at the short-term. A fixed-effects model including 193 genu OA patients (97 in the BoNT-A therapy group and 96 in the placebo group) revealed an MD of −5.37 (95% CI: −7.xviii to −3.57 (P<0.00001) and indicated that BoNT-A IA injection therapy resulted in lower WOMAC questionnaire scores (Figure 4a).

Forest plots showing changes in (a) WOMAC questionnaire score short-term (≤4 weeks) and (b) WOMAC questionnaire score long-term (≥8 weeks) in the handling studies.

BoNT-A: Botulinum toxin type A, SD: standard deviation, Four: inverse variance, CI: confidence interval, WOMAC: Western Ontario & McMaster Universities Osteoarthritis Index.

Measurements at long-term (≥eight weeks)

V studies including v comparisons were used to analyze results for WOMAC questionnaire score at long-term. A random-effects model including 314 articulatio genus OA patients (158 in the BoNT-A therapy grouping and 156 in the placebo group) revealed an MD of −7.x (95% CI: −10.89 to −3.31 (P = 0.0002) and indicated that BoNT-A IA injection therapy revealed a significant subtract in the long-term WOMAC questionnaire scores (Figure 4b).

Adverse events

No serious adverse events, such as expiry, sensory dysfunction or new lower limb motor dysfunction, anaphylactic reaction to the injection, or inflammation at the injection site occurred during these studies. No transient musculus weakness was found in any of the groups.

Discussion

Human knee OA is a common joint affliction that affects 250 million patients around the earth.¹⁸ Notwithstanding, the health organizations have not canonical whatsoever unmarried therapeutic method every bit the standard treatment method for genu OA. Joint replacement surgery is an option for patients with advanced stages of the illness.^nineteen Recently, there is increased interest in the new medical applications of BoNT-A. Although the clinical application of BoNT-A seems promising, there is yet insufficient testify on its therapeutic effects.

Our meta-analysis included five studies including 314 patients comparing the efficacy and safety of BoNT-A IA injection (100U/200U) to a placebo in treating men with knee OA in both the short-term (≤iv weeks) and long-term (≥8 weeks) periods. The analysis institute that BoNT-A IA injection had a greater improvement than placebo in terms of the VAS pain scale and WOMAC questionnaire score in both the brusque-term and long-term treatment periods. Additionally, in the studies of Bao et al.^xvi and Mendes et al.,¹⁷ BoNT-A IA injection demonstrated an acceptable safety profile, with improvements in the Physical Component Summary-36, Mental Component Summary-36, and ultrasound measurement of synovial hypertrophy.

The mechanism of action of BoNT-A is to inhibit the release of acetylcholine from the exocytosis of motor nervus endings.^xx This makes it useful for the treatment of several pathological weather involving excessive muscle contraction, such as paralysis, painful dyskinesia, and other pain weather condition.²¹ However, increasing show has indicated that BoNT-A can relieve pain by inhibiting the release of selective neuropeptide transmitters, thus directly reducing peripheral sensitization and indirectly reducing central sensitization.²²

For safety, the study showed that no serious adverse events occurred, such every bit death, sensory dysfunction or new lower limb motor dysfunction, anaphylactic reaction to the injection, or inflammation of the injection site. No transient muscle weakness was establish in whatever of the groups. Other agin events were well tolerated and the relevant data were lacking from the included studies. Still, Dutra²³ institute that BoNT-A injection in the masseter of mice can significantly damage the mandibular condylar cartilage and subchondral bone and the damage is non transient. Therefore, whether long-term use of BoNT-A will lead to histological changes still requires boosted high-quality RCTs to show. As for the injection road, all of the included RCTs injected BoNT-A into the articular cavity, and there have been no studies focusing on the difference between intra-articular injection and intra-muscular injection.

This meta-analysis includes findings only from RCTs. From a scientific point of view, the results of this analysis are very important. However, the number of included studies is small. Option bias, subjective factors, and publication bias may as well touch on the final results of our written report. These factors may lead to bias. More high-quality trials with larger sample sizes are needed to verify the efficacy and safety of BoNT-A IA injection therapy for painful knee OA.

Conclusion

This meta-assay suggests that Botulinum Toxin Type A is an effective and prophylactic approach for the handling of painful genu OA. Withal, large-scale multicenter RCTs are withal needed to farther ostend our findings.

Declaration of conflicting interest

The authors declare that there is no conflict of interest.

Funding

This research received no specific grant from whatsoever funding agency in the public, commercial, or not-for-profit sectors.

References

ane. Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med 2010; 26: 355–369. DOI: ten.1016/j.cger.2010.03.001. [PMC complimentary article] [PubMed] [Google Scholar]

2. Woolf Advertising, Akesson Chiliad. Understanding the burden of musculoskeletal conditions. The burden is huge and not reflected in national health priorities. BMJ 2001; 322: 1079–1080. DOI: x.1136/bmj.322.7294.1079. [PMC gratis article] [PubMed] [Google Scholar]

iii. Ikeuchi M, Izumi M, Aso Ket al. Clinical characteristics of pain originating from intra-articular structures of the knee articulation in patients with medial genu osteoarthritis. Springerplus 2013; 2: 628. DOI: 10.1186/2193-1801-2-628. [PMC free commodity] [PubMed] [Google Scholar]

four. Birmingham TB, Kramer JF, Kirkley Aet al. Knee bracing for medial compartment osteoarthritis: effects on proprioception and postural control. Rheumatology (Oxford) 2001; 40: 285–289. DOI: x.1093/rheumatology/40.3.285. [PubMed] [Google Scholar]

five. Hochberg MC, Altman RD, April KTet al. American Higher of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and human knee. Arthritis Care Res (Hoboken) 2012; 64: 465–474. [PubMed] [Google Scholar]

vi. Felson DT, Lawrence RC, Dieppe PAet al. Osteoarthritis: new insights. Function one: the illness and its take a chance factors. Ann Intern Med 2000; 133: 635–646. DOI: 10.7326/0003-4819-133-8-200010170-00016. [PubMed] [Google Scholar]

7. Juni P, Hari R, Rutjes AWet al. Intra-articular corticosteroid for genu osteoarthritis. Cochrane Database Syst Rev 2015; x: Cd005328. DOI: 10.1002/14651858.CD005328.pub3. [PMC free commodity] [PubMed] [Google Scholar]

eight. Courseau M, Salle PV, Ranoux Det al. Efficacy of intra-articular botulinum toxin in osteoarticular joint hurting: a meta-analysis of randomized controlled trials. Clin J Hurting 2018; 34: 383–389. DOI: 10.1097/ajp.0000000000000538. [PubMed] [Google Scholar]

9. Wu T, Song HX, Dong Yet al. Intra-articular injections of botulinum toxin a for refractory articulation pain: a systematic review and meta-analysis. Clin Rehabil 2017; 31: 435–443. DOI: x.1177/0269215516644951. [PubMed] [Google Scholar]

10. Jadad A. Randomised controlled trials. London: BMJ Publishing Grouping, 1998. [Google Scholar]

11. DerSimonian R, Laird Due north. Meta-analysis in clinical trials. Control Clin Trials 1998; 3: 177–188. [PubMed] [Google Scholar]

12. Higgins JP, Thompson SG, Deeks JJet al. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557–560. DOI: 10.1136/bmj.327.7414.557. [PMC free article] [PubMed] [Google Scholar]

13. Mahowald ML, Krug HE, Singh JAet al. Intra-articular Botulinum Toxin Blazon A: a new approach to treat arthritis joint pain. Toxicon 2009; 54: 658–667. DOI: x.1016/j.toxicon.2009.03.028. [PubMed] [Google Scholar]

14. Hsieh LF, Wu CW, Chou CCet al. Effects of botulinum toxin landmark-guided intra-articular injection in subjects with knee osteoarthritis. PM R 2016; 8: 1127–1135. DOI: 10.1016/j.pmrj.2016.05.009. [PubMed] [Google Scholar]

fifteen. Arendt-Nielsen 50, Jiang GL, DeGryse Ret al. Intra-articular onabotulinumtoxinA in osteoarthritis knee hurting: event on human mechanistic hurting biomarkers and clinical hurting. Scand J Rheumatol 2017; 46: 303–316. DOI: 10.1080/03009742.2016.1203988. [PubMed] [Google Scholar]

xvi. Bao X, Tan JW, Flyzik Met al. Effect of therapeutic do on knee osteoarthritis later on intra-articular injection of botulinum toxin blazon A, hyaluronate or saline: a randomized controlled trial. J Rehabil Med 2018; 50: 534–541. DOI: 10.2340/16501977-2340. [PubMed] [Google Scholar]

17. Mendes JG, Natour J, Nunes-Tamashiro JCet al. Comparison between intra-articular Botulinum toxin blazon A, corticosteroid, and saline in knee osteoarthritis: a randomized controlled trial. Clin Rehabil 2019; 33: 1015–1026. DOI: ten.1177/0269215519827996. [PubMed] [Google Scholar]

18. Mills K, Hubscher Chiliad, O'Leary Het al. Electric current concepts in joint pain in human knee osteoarthritis. Schmerz 2019; 33: 22–29. DOI: 10.1007/s00482-018-0275-ix. [PubMed] [Google Scholar]

19. Nielsen FK, Egund Northward, Jorgensen Aet al. Risk factors for joint replacement in knee osteoarthritis; a 15-year follow-up study. BMC Musculoskelet Disord 2017; 18: 510. DOI: 10.1186/s12891-017-1871-z. [PMC free article] [PubMed] [Google Scholar]

20. Simpson LL. The origin, construction, and pharmacological activity of botulinum toxin. Pharmacol Rev 1981; 33: 155–188. [PubMed] [Google Scholar]

21. Lew HL, Lee EH, Castaneda Aet al. Therapeutic utilize of botulinum toxin blazon A in treating neck and upper-back hurting of myofascial origin: a pilot study. Curvation Phys Med Rehabil 2008; 89: 75–80. DOI: 10.1016/j.apmr.2007.08.133. [PubMed] [Google Scholar]

22. Aoki KR. Review of a proposed mechanism for the antinociceptive action of botulinum toxin blazon A. Neurotoxicology 2005; 26: 785–793. DOI: 10.1016/j.neuro.2005.01.017. [PubMed] [Google Scholar]

23. Dutra EH, Yadav South. The effects on the mandibular condyle of Botox injection into the masseter are not transient. Am J Orthod Dentofacial Orthop 2019; 156: 193–202. DOI: 10.1016/j.ajodo.2018.08.023. [PMC gratuitous commodity] [PubMed] [Google Scholar]

---

Articles from The Journal of International Medical Research are provided here courtesy of SAGE Publications

---

krusesmagre.blogspot.com

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783274/

Share this post