Comparative Efficacy of Intra-Articular Injection, Physical Therapy, and Combined Treatments on Pain, Function, and Sarcopenia Indices in Knee Osteoarthritis: A Network Meta-Analysis of Randomized Controlled Trials

Abstract

Knee osteoarthritis (KOA) is associated with a high risk of sarcopenia. Both intra-articular injections (IAIs) and physical therapy (PT) exert benefits in KOA. This network meta-analysis (NMA) study aimed to identify comparative efficacy among the combined treatments (IAI+PT) in patients with KOA. Seven electronic databases were systematically searched from inception until January 2023 for randomized controlled trials (RCTs) reporting the effects of IAI+PT vs. IAI or PT alone in patients with KOA. All RCTs which had treatment arms of IAI agents (autologous conditioned serum, botulinum neurotoxin type A, corticosteroids, dextrose prolotherapy (DxTP), hyaluronic acid, mesenchymal stem cells (MSC), ozone, platelet-rich plasma, plasma rich in growth factor, and stromal vascular fraction of adipose tissue) in combination with PT (exercise therapy, physical agent modalities (electrotherapy, shockwave therapy, thermal therapy), and physical activity training) were included in this NMA. A control arm receiving placebo IAI or usual care, without any other IAI or PT, was used as the reference group. The selected RCTs were analyzed through a frequentist method of NMA. The main outcomes included pain, global function (GF), and walking capability (WC). Meta-regression analyses were performed to explore potential moderators of the treatment efficacy. We included 80 RCTs (6934 patients) for analyses. Among the ten identified IAI+PT regimens, DxTP plus PT was the most optimal treatment for pain reduction (standard mean difference (SMD) = -2.54) and global function restoration (SMD = 2.28), whereas MSC plus PT was the most effective for enhancing WC recovery (SMD = 2.54). More severe KOA was associated with greater changes in pain (β = -2.52) and WC (β = 2.16) scores. Combined IAI+PT treatments afford more benefits than do their corresponding monotherapies in patients with KOA; however, treatment efficacy is moderated by disease severity.

Keywords: injection; meta-analysis; mobility; osteoarthritis; pain; physical therapy; sarcopenia.

Figure 1

PRISMA flowchart of the study selection.

Figure 2

Network plot of direct comparisons among treatments for (A) pain, (B) global function, and (C) walking capability. The lines between nodes indicate direct comparisons in other studies. The size of each node is proportional to the number of participants. The thickness of each line is proportional to the number of studies denoted on the line. ACS, autologous conditioned serum; BoNTA, botulinum toxin type A; CS, corticosteroid; DxTP, dextrose prolotherapy; HA, hyaluronic acid; MSC, mesenchymal stem cell; OZ, ozone; PRP, platelet-rich plasma; PRGF, plasma rich in growth factor; PT, physical therapy; SVF, stromal vascular fraction; UC, usual care.

Figure 3

Forest plot summarizing the effects of treatment regimens on pain reduction for the entire follow-up duration. SMD, standardized mean difference; CI, confidence interval; SUCRA, surface under the cumulative ranking curve; ACS, autologous conditioned serum; BoNTA, botulinum toxin type A; CS, corticosteroid; DxTP, dextrose prolotherapy; HA, hyaluronic acid; MSC, mesenchymal stem cell; OZ, ozone; PRP, platelet-rich plasma; PRGF, plasma rich in growth factor; PT, physical therapy; UC, usual care.

Figure 4

Forest plot summarizing the effects of treatment regimens on global function restoration for the entire follow-up duration. SMD, standardized mean difference; CI, confidence interval; SUCRA, surface under the cumulative ranking curve; ACS, autologous conditioned serum; BoNTA, botulinum toxin type A; CS, corticosteroid; DxTP, dextrose prolotherapy; HA, hyaluronic acid; MSC, mesenchymal stem cell; OZ, ozone; PRP, platelet-rich plasma; PRGF, plasma rich in growth factor; PT, physical therapy; SVF, stromal vascular fraction; UC, usual care.

Figure 5

Forest plot summarizing the effects of treatment regimens on walking capability recovery for the entire follow-up duration. SMD, standardized mean difference; CI, confidence interval; SUCRA, surface under the cumulative ranking curve; CS, corticosteroid; DxTP, dextrose prolotherapy; HA, hyaluronic acid; MSC, mesenchymal stem cell; OZ, ozone; PRP, platelet-rich plasma; PRGF, plasma rich in growth factor; PT, physical therapy; UC, usual care.

Figure 6

Compliance and adverse events of intra-articular infection regimens. Data concerning treatment-related (A) withdrawals and (B) adverse events were pooled using inverse variance weighting methods. OR, odds ratio; CI, confidence interval; ACS, autologous conditioned serum; BoNTA, botulinum toxin type A; CS, corticosteroid; DxTP, dextrose prolotherapy; HA, hyaluronic acid; MSC, mesenchymal stem cell; OZ, ozone; PRP, platelet-rich plasma; PRGF, plasma rich in growth factor; PT, physical therapy; SVF, stromal vascular fraction; UC, usual care.