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.

Effects of the combination of various pharmacological treatments and exercise on knee osteoarthritis: a systematic review and network meta-analysis

“…However, the findings could not be generalized because only soccer athletes with early osteoarthritis were included ( 17 ). Liao et al ( 18 ) performed a network meta-analysis to investigate the efficacy of the combination of injection therapies and physical therapies. The results supported the use of MSC, dextrose, PRP, PRGF, and botulinum toxin A in combination with physical therapy.…”

Clinical and Biochemical Implications of Hyaluronic Acid in Musculoskeletal Rehabilitation: A Comprehensive Review

“…Their specific emphasis was on assessing the combined therapy's influence on pain levels, overall functional improvement, and walking capacity. Through this approach, they aimed to establish the most effective treatment option by ranking the effectiveness of each combined therapy regimen and exploring any factors that might influence treatment outcomes [77].…”

“…In the specific case of the combination of intra-articular injections of HA and physical therapy, it was observed that this treatment appeared to be more effective in reducing pain compared with physical therapy alone. Additionally, it allowed for better walking capacity in the short term, both compared with physical therapy alone and in comparison with other intra-articular injections [77].…”

Effects of high tibial osteotomy compared with unicondylar knee arthroplasty on the surgical site wound infection and pain in patients with medial knee osteoarthritis

“… 6 , 7 Treatment options for KOA range from non‐surgical interventions in the early stages to surgical treatments in advanced stages. 8 , 9 Most patients requiring surgery have medial compartment KOA, with high tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA) as common surgical options. 10 , 11 , 12 …”

“…6,7 Treatment options for KOA range from non-surgical interventions in the early stages to surgical treatments in advanced stages. 8,9 Most patients requiring surgery have medial compartment KOA, with high tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA) as common surgical options. [10][11][12] HTO corrects joint deformities and abnormal force lines in the knee by shifting the load-bearing axis from the damaged medial compartment to the undamaged lateral compartment, thereby relieving pain.…”