Research Review By Dr. Joshua Plener©


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Date Posted:

April 2021

Study Title:

Estimating Contextual Effect in Nonpharmacological Therapies for Pain in Knee Osteoarthritis: A Systematic Analytic Review


Chen A, Shrestha S, Collins J et al.

Author's Affiliations:

Orthopaedic and Arthritis Center for Outcomes Research (OrACORe) and Policy and Innovation evaluation in Orthopaedic Treatments (PIVOT) Center, Department of Orthopaedic Surgery, Harvard Medical School, Boston, MA, USA

Publication Information:

Osteoarthritis and Cartilage 2020; 28(9): 1154-1169.

Background Information:

Knee osteoarthritis (OA) is characterized by pathological damage to the articular cartilage, meniscus and subchondral bone with osteophyte formation and synovial proliferation. Current treatments attempt to decrease clinical symptoms experienced by patients, which include pain and functional limitations.

Effective first line treatment for knee OA includes nonpharmacological and nonsurgical therapies, however patients generally underutilize these interventions (1). Potential barriers that have been reported include clinicians’ perceived lack of expertise, perceived lack of evidence-based treatment, and suboptimal organization of care (1). Furthermore, in order to understand the total therapeutic effect of treatment for knee OA (2-4), an understanding of both the direct physiological and contextual effects of treatment is required. Examples of contextual factors include the placebo effect, changes attributable to natural history, and effects of co-therapies. Gaining a deeper understanding of this will help improve the management of knee OA.

This systematic review is a first attempt to quantify the role of contextual factors in nonpharmacological, nonsurgical treatments for knee OA patients, comparing baseline and follow-up pain outcomes for active and placebo treatment groups.

Pertinent Results:

Out of 5,321 citations in the initial search, 27 studies remained. However, one study was excluded after scoring below 5 on the PEDro quality assessment scale (5) and only one other study looked at exercise (6), which was excluded, since a meta-analysis could not be performed. Therefore, 25 studies were ultimately included which examined acupuncture and topical energy modalities (TEM), which consisted of ultrasound, TENS and laser modalities.

The acupuncture studies included a total of 1,653 subjects, while the TEM studies included 572 subjects. A co-therapy was reported in 10 studies, 7 of which were exercise, 2 were NSAIDs and 1 was the administration of a placebo tablet.

Both acupuncture and TEM study groups had high overall heterogeneity and the PEDro scores of the final studies ranged from 7 to 10 with a mean of 8.

A meta-analysis was performed to evaluate the contribution of contextual factors to the total analgesic effects experienced by knee OA patients receiving acupuncture or TEM treatments.

Acupuncture results:
Effect sizes for the contextual effect ranged from 0.02 to 2.0 and the effect sizes for the total treatment effect ranged from 0.54 to 3.94. Across the acupuncture studies, contextual factors accounted for about 61% of pain relief experienced by patients receiving treatment.

TEM results:
Effect sizes for the contextual effect ranged from 0.08 to 6.05 and the range of effect sizes for the total treatment effect ranged from 0.19 to 8.68. Across TEM studies that examined laser, ultrasound and TENS modalities, 69% of the total treatment effect was a result of contextual effects.

The sensitivity analyses performed revealed similar results as above.

Clinical Application & Conclusions:

The results of this systematic review and meta-analysis demonstrate that a substantial proportion of the analgesic effect experienced by patients receiving acupuncture or TEM treatments for knee OA appear to be the result of contextual effects. This was the first study to quantify the role of nonpharmacological, nonsurgical treatments to knee OA specifically, however similar results were found in Zou et al. who investigated OA of the spine, hip, knee, hand, foot, and TMJ (7). Furthermore, this study and previous studies support the role of placebo as being one of, if not the most important contextual effect (8).

The role of contextual factors on the total therapeutic effect mirrors findings of prior research investigating other musculoskeletal conditions. There is enough research now to demonstrate that contextual factors play a large role in patient care. This provides an interesting and exciting opportunity for clinicians as the clinical environment and the clinician-patient interaction has been demonstrated to be extremely important in patient recovery.

Study Methods:

The following databases were searched encompassing all treatments mentioned in the Osteoarthritis Research Society International (OARSI) guidelines for nonpharmacological interventions (9), as well as associated MESH terms (10): MEDLINE, Embase, Web of Science, CINAHL, and Cochrane Central.

Eligibility for study inclusion:
The first author identified commonly used nonpharmacological, nonsurgical therapies for knee OA by searching PubMed. This search identified exercise therapy, laser therapy, ultrasound therapy, acupuncture therapy, and transcutaneous electrical nerve stimulation (TENS) as the five most frequently studied modalities. All included studies were required to have one of these therapeutic approaches.

Inclusion criteria:
  • The study was a randomized controlled trial
  • The study included a placebo arm
  • The study only enrolled knee OA individuals who have not received a total knee replacement
  • The study involved an active treatment modality that was either exercise, laser, ultrasound, acupuncture or TENS therapy
  • The study reported a pain outcome
  • The study included a follow-up assessment of 1-3 months after baseline measurements
  • The study reported an improvement of pain after baseline
  • The study had a published full-length manuscript that could be retrieved
  • The study received a PEDro scale quality assessment score greater then 5 points. The PEDro scale evaluates criteria such as study eligibility, randomization, and blinding on a 10-point scale. Moderate to high-quality studies are a score of 6 or more (11).
  • The study was published in English
For this systematic review, “placebo treatment” was considered an intervention that physically resembled the active treatment without delivering the therapy.

Data Analysis:
  • Heterogeneity tests: I2 statistics were used to assess study heterogeneity where larger values indicate greater heterogeneity.
  • Calculating effect size and proportion of total treatment effect attributable to contextual effect (PCE): For each study the effect size was calculated in order to understand the total treatment effect. The contextual effect was calculated by dividing the mean difference between follow-up measurements and baseline by the pooled standard deviation of change between active and placebo arms
  • Estimating the PCE: In order to determine the proportion of improvement due to contextual effects, the authors divided the mean pain improvement between baseline and follow-up of the placebo group by the mean improvement in pain of the active group.

Study Strengths / Weaknesses:

  • This was the first attempt to quantify the role of contextual factors in nonpharmacological, nonsurgical treatments for knee OA patients. This is an important area of research for many clinical conditions.
  • The findings of this study provide clinicians with an understanding of how important contextual factors are in the total treatment effect that patients experience. However, further research is required on how to best utilize these effects.
  • Despite the strict selection criteria, there was still wide variation in study designs such as enrollment criteria of knee OA.
  • There was large heterogeneity between studies which may reduce the comparability aspect of the studies.
  • The findings of this systematic review on knee OA pain cannot be generalized to functional measures, despite the association between knee OA pain and knee OA disability (12).
  • The meta-analysis did not include any exercise-based approaches, as only one trial included a placebo control which is necessary to evaluate the contextual effects.

Additional References:

  1. Selten EMH, Vriezekolk JE, Nijhof MW, et al. Barriers impeding the use of non-pharmacological, non-surgical care in hip and knee osteoarthritis: The views of general practitioners, physical therapists, and medical specialists. J Clin Rheumatol 2017; 23(8): 405-410.
  2. Bennell KL, Egerton T, Martin J, et al. Effect of physical therapy on pain and function in patients with hip osteoarthritis: A randomized clinical trial. JAMA 2014; 311(19): 1987-1997.
  3. De Groef A, Van Kampen M, Vervloesem N, et al. Myofascial techniques have no additional beneficial effects to a standard physical therapy programme for upper limb pain after breast cancer surgery: A randomized controlled trial. Clin Rehabil 2017; 31(12): 1625-1635.
  4. Garcia AN, Costa L, Hancock MJ, et al. Mckenzie method of mechanical diagnosis and therapy was slightly more effective than placebo for pain, but not for disability, in patients with chronic non-specific low back pain: A randomised placebo controlled trial with short and longer term follow-up. Br J Sports Med 2018; 52(9): 594-600.
  5. Shen X, Zhao L, Ding G, et al. Effect of combined laser acupuncture on knee osteoarthritis: A pilot study. Lasers Med Sci 2009; 24(2): 129-136.
  6. Bennell KL, Hinman RS, Metcalf BR, et al. Efficacy of physiotherapy management of knee joint osteoarthritis: A randomised, double blind, placebo controlled trial. Ann Rheum Dis 2005; 64(6): 906-912.
  7. Zou K, Wong J, Abdullah N, et al. Examination of overall treatment effect and the proportion attributable to contextual effect in osteoarthritis: Meta analysis of randomised controlled trials. Annals of the Rheumatic Diseases 2016; 75(11): 1964.
  8. Zhang W, Robertson J, Jones AC, et al. The placebo effect and its determinants in osteoarthritis: Meta-analysis of randomised controlled trials. Ann Rheum Dis 2008; 67(12): 1716-1723.
  9. Mcalindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage 2014; 22(3): 363-388.
  10. National Center for Biotechnology Information. MeSH: Medical subject headings. Available from
  11. Dziedzic KS, Hill JC, Porcheret M et al. New models for primary care are needed for osteoarthritis. Phys Ther 2009; 89(12): 1371-1378.
  12. Cubukcu D, Sarsan A and Alkan H. Relationships between pain, function and radiographic findings in osteoarthritis of the knee: A cross-sectional study. Arthritis 2012; 2012: 984060.

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