Abstract
Context
Chronic non-cancer pain (CNCP) is associated with disability, poor quality of life (QOL), and failure to return to work (RTW). Osteopathic manipulative treatment (OMT) or osteopathic manual therapy (OMTh) are increasingly offered to patients with CNCP; however, the existing systematic reviews and meta-analyses in the literature that explore the effectiveness of OMTh have major limitations.
Objective
To systematically evaluate the quality of evidence documenting the effectiveness of OMTh for patients with CNCP using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, and to evaluate the efficacy of OMTh in patients with CNCP through a meta-analysis of pooled data from previous studies.
Methods
We searched online the databases Ovid, MEDLINE, Embase, OSTMED.DR, EMCare, Allied and Complementary Medicine Database (AMED), Physiotherapy Evidence Database (PEDro), and Cochrane Central Register of Controlled Trials (CENTRAL), as well as the bibliographic references of previous systematic review articles evaluating OMTh for pain severity, disability, QOL, or RTW outcomes. Eligibility included randomized controlled trials methodology, CNCP patients 18 years or older, use of previously validated assessment tools, use of OMTh as an active or combination intervention, and presence of a control or comparison group. We pooled studies based on the homogeneity between OMT comparator treatment and outcomes. Risk of bias was assessed with the Cochrane risk of bias tool and the quality of evidence was determined with GRADE.
Results
Sixteen randomized controlled trials (n=1158 patients) were eligible for data extraction. Moderate quality evidence showed that OMTh vs. standard care was significantly associated with a reduction in pain [standardized mean difference (95% CI)=[−.37 (−.58, −.17)] and disability [−.28 (−.46, −.10)], as well as improved QOL [.67 (.29, 1.05)]. Moderate quality evidence showed that OMTh plus exercise vs. exercise only was significantly associated with reduction in pain severity [−1.25 (−1.67, −.83)] and disability [−1.15 (−1.57, −.74)]. Moderate quality evidence showed that using visceral OMTh vs. general OMTh was significantly associated with reduction in pain severity [−.74 (−1.09, −.39)] and disability [−.52 (−.91, −.13)]. In comparison to physiotherapy, gabapentin, and OMTh plus gabapentin, OMTh did not show any significant effect for any of the outcomes. OMTh vs. standard care did not show significant improvement in RTW at 12 weeks, although the effect was significant at 8 weeks after OMTh.
Conclusion
Moderate quality evidence suggests that OMTh is effective for CNCP patients. There was a significant association between visceral OMTh and reduced pain severity and disability. More robust, high-quality randomized controlled trials with larger sample sizes are required to further explore the effectiveness of the OMTh in the management of CNCP.
Chronic noncancer pain (CNCP) affects approximately 19% of the general population1-3 and includes a range of conditions that involve mechanical (eg, low back pain, osteoarthritis) and neuropathic (eg, fibromyalgia) disorders. CNCP interferes with activities of daily living, contributes to psychologic distress, and is associated with disability and work loss,2-5 causing substantial socioeconomic impact.6-8 CNCP is also among the most common reasons for patients to consult general practitioners and specialist pain clinics.5,6 Management of CNCP is multi-disciplinary: combination treatments are reported to provide better pain relief and functional outcomes.9,10 Depending on the underlying cause, treatments for CNCP include pharmacologic intervention, psychotherapy, and physical treatments such as physiotherapy, chiropractic treatments, massage therapy, and osteopathic manipulative treatment (OMT) or osteopathic manual therapy (OMTh).10-12 Although the same principles are followed in the manual treatment approach, OMT is performed by physicians, whereas OMTh is performed by nonphysicians.
OMTh is increasingly employed to manage CNCP13,14 and, like other manual therapies, is known to alter biomechanical, neurophysiologic, and various other patient-related factors through anatomic and physiologic connections to the autonomic nervous system.15-18 OMTh requires a comprehensive understanding of anatomy and physiology and, based on osteopathic principles, uses that knowledge to mobilize and influence the patient's body. The 4 main principles of osteopathy19-21 are that the body is a unit and the person is a unit of body, mind, and spirit; the body is capable of self-regulation, self-healing, and health maintenance; structure and function are reciprocally interrelated; and rational treatment is based on an understanding of the basic principles of body unity, self-regulation, and the interrelationship of structure and function.
Although OMTh is increasingly offered to patients to help manage CNCP, it is still widely underused, and research into its benefits remains in its infancy.22-24 Previous systematic reviews and meta-analyses exploring the effectiveness of OMTh have had a variety of limitations such as language restriction,25 narrow search strategies,25 inclusion criteria not being restricted to randomized controlled trials (RCTs)26 or to OMTh topics,26,27 inclusion of studies with both acute and chronic pain,28-30 or inclusion of duplicate studies (such as substudies of larger trials).26 Given these limitations, interpreting the results of reviews and meta-analyses in the current literature and drawing conclusions about the effectiveness of OMTh can be challenging. Therefore, larger, high-quality data exploring the effectiveness of OMTh in the management of CNCP is sorely needed. Our goal was to conduct a systematic review and meta-analysis to explore the effectiveness of OMTh in CNCP and its effect on pain reduction, functional impairment, quality of life (QOL), and return to work (RTW). We also evaluated the quality of evidence in a thorough and consistent manner using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.31,32
Methods
We conducted our meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.33 The study protocol was registered with Prospero (Registration #CRD42019125659).
The keywords for our searches were developed using the MeSH word analyzer (http://MeSH.med.yale.edu/). Searches were conducted starting in July 2018 and were updated in July 2019. We developed a broad search strategy using Ovid to search MEDLINE, Embase, OSTMED.DR, EMCare, Allied and Complementary Medicine Database (AMED), Physiotherapy Evidence Database (PEDro), and Cochrane Central Register of Controlled Trials (CENTRAL) databases. The bibliographic references of previous systematic reviews23-29 were also searched for eligible trials. The Ovid MEDLINE literature search strategy is provided in the eAppendix. Our eligibility criteria included randomized controlled trials (RCTs) that had enrolled CNCP patients 18 years of age or older, employed OMTh as an active or combination intervention, and compared OMTh to any other intervention or control. Eligible trials explored the effectiveness of OMTh on pain severity, disability, QOL, or RTW outcomes and were reported with previously validated tools. We excluded RCTs that enrolled <10 participants per arm at baseline or if the authors reported a composite score. Studies with a focus on cancerous pain, pain developed during pregnancy, headaches, pain due to gynecologic abnormalities, purely irritable bowel syndrome (IBS), or other visceral pain such as prostatitis were also excluded. We excluded crossover trials because of the possibility of carry-over effect and because methodologic challenges limit their applicability.34,35 Because OMTh is governed by a set of principles and uses a combination of methods to treat the body,30 we excluded studies that were specifically investigating a single technique without employing additional use of general OMTh. An amendment in our original Prospero protocol was made because we initially excluded pilot trials but found we did not have enough eligible studies and therefore broadened our inclusion criteria to include pilot trials.
Data Collection and Analysis Plan
Title and abstract, full text screening, data abstraction, and risk of bias (ROB) were compiled in duplicate and independently by a team of reviewers (Y.R., H.F., J.B., A.B., A.A.). We extracted information related to the trial design, patient demographics, interventions, outcomes, and ROB. When possible, we pooled studies according to the type of OMTh and comparator for each outcome. OMTh is applied according to an individual's condition and at the discretion of the examiner with variations; therefore, for pooling purposes we considered relative similarities between OMTh, treatment comparators, and outcomes across studies.35,36 We reported results with standardized mean difference (SMD) with a 95% confidence interval (CI) interval. Albers et al37 and Licciardone et al38 were 3-arm studies and, based on the similarities between the OMTh applied and comparators, respectively, we merged the 2 arms. If we had 2 studies in the pooled analysis, we reported results with fixed effect model (FEM); if we had more than 2 studies in the pooled analysis, we reported results with random effect model (REM). For FEM, we also checked with REM for change in variability. We analyzed data with change scores, but in cases where change scores were not reported, we pooled with the final score according to Cochrane's criteria.35 If quantitative pooling was not possible, we reported outcomes descriptively.
Quality of Evidence
The quality of evidence was assessed using GRADE,31,32 which consists of 5 components: ROB, inconsistency, imprecision, publication bias, and indirectness.
Risk of bias: ROB was analyzed using a modified Cochrane ROB tool on the following components: random sequence generation, allocation concealment, blinding of participants, healthcare provider, outcome assessors, and dropout rates.35
Heterogeneity (inconsistency): Heterogeneity of the pooled studies was determined by visual inspection of forest plots and using the I² statistic. For heterogeneity, we used a cutoff of 60% or if on visual inspection of the forest plot there was inconsistency in the effect estimates of individual studies.35
Publication bias: We did not have 10 or more studies in any pooled analysis and therefore could not assess publication bias in the pooled analysis.
Indirectness and inconsistency: The clinical characteristics of the participants and width of the confidence interval, respectively, were assessed for indirectness and inconsistency.
Sensitivity and Subgroup Analysis
We did not have enough studies to perform subgroup analysis according to the a priori specified in our Prospero protocol. We pooled studies comparing the effectiveness of OMTh against sham and OMTh against standard care (SC). Our rationale was based on the fact that studies with sham comparison allowed patients to continue usual treatment; therefore, we explored subgroup analysis to assess whether our rationale to pool studies with sham treatment and SC was justifiable. We also performed a sensitivity analysis to compare to previous systematic reviews by pooling studies according to low back pain (LBP) only, while ignoring the differences in control treatments/comparators.
The statistical analysis was performed with Review Manager 5.3 (Review Manager [RevMan] version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).
Results
Our searches from all databases yielded 2956 studies for screening (Figure 1), out of which 16 studies were eligible for data extraction. A summary of the included studies is given in Table 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.
Baseline Characteristics of the Included Studies
| Author/ Year | Age, mean (SD) | Gender- female (%) | Pain region | Were patients with comorbid psychologic and medical conditions included? | Was disability/ litigation considered part of exclusion criteria? | Were other medications allowed? | Duration of trial or follow-up period (days) | Number of participants in intervention group | Number of participants in control or comparison groups |
|---|---|---|---|---|---|---|---|---|---|
| Albers 201837 | 54.9 (13.1) | 3.3 | Fibromyalgia | No | NR | NR | 84 | 34 | 14 |
| Altinbilek 2018 | 54.8 (8.4) | 89.4 | Knee OA | Yes | NR | No; except for paracetamol | 151 | 44 | 41 |
| Burton 200049 | 41.9 (10.6) | 52.5 | LBP/ LDH | Yes | Yes | NR | 365 | 15 | 15 |
| Chown 200852 | 43.6 | 58.5 | Chronic LBP | Yes | NR | Steroids were not allowed | 365 | 39 | 59 |
| Cuccia 201043 | 39.5 (13.1) | 58.7 | TMD | No | NR | NR | 168 | 25 | 25 |
| Knebl 200242 | 65-85 | 62.1 | Chronic shoulder pain | Yes | NR | NR | 105 | NR | NR |
| Licciardone 200338 | 49.9 (8.0) | 64.6 | Chronic nonspecific LBP | Yes | Yes | Yes | 84 | 32 | 34 |
| Licciardone 201350 | 40.5 (16.3) | 62.5 | Chronic nonspecific LBP | Yes | Yes | Yes | 56 | 230 | 225 |
| Marske 201844 | 51.2 | 93.2 | Fibromyalgia | No | NR | NR | 42 | 11/10 | 8 |
| Marti-Salvador 201848 | 18-60 | NR | Chronic nonspecific LBP | No | NR | No | 56 | 33 | 33 |
| Papa 201245 | 77 (6.7) | 70.5 | Chronic nonspecific body pain | Yes | NR | NR | 42 | 37 | 35 |
| Schwerla 200840 | 35.4-54.2 | 75.6 | Chronic nonspecific neck pain | No | Yes | NR | 84 | 21 | 16 |
| Silva 201846 | 25.4 (8.29) | NR | Non-specific neck pain | No | No | No | 7 | 14 | 14 |
| Stepnik 201839 | 23-53 | 83.9 | Chronic Neck Pain | No | No | NR | NR | 16 | 15 |
| Tamer 201747 | 39.9 (5.1) | 53.9 | Chronic nonspecific LBP | No | Yes | No | 42 | 20 | 19 |
| Vismara 201251 | 43.7 (9.8) | 100 | Chronic LBP | No | Yes | NR | NR | 10 | 11 |
Abbreviations: LBP, low back pain; LDH, lumbar disc herniation; NR, not reported; OA, osteoarthritis; TMP, temporomandibular disorder.
The collective sample size from all eligible studies was 1158. The median age of the eligible population was 43.3 years, with a range of 23 to 78 years. Chronic LBP was the most prevalent pain type among the included studies.39-45 Three studies explored the effectiveness of OMTh in the treatment of neck pain,39,40,46 and other studies explored the effectiveness of OMTh in knee arthritis,41 shoulder pain,42 temporomandibular joint (TMJ) pain,43 fibromyalgia,37,44 or nonspecific musculoskeletal pain.45 Except for 7 studies,39,40,43,44,46-48 all others excluded patients with other medical or psychologic conditions. Six studies38,40,47,49-51 excluded patients with disability claims or with ongoing litigation. Six studies specifically stated excluding patients with cancer.37,38,40,41,48,50 Only 2 authors48,50 accounted for missing data in their RTCs.
Description of OMTh and treatments are given in Table 2. Overall, methods of osteopathic treatments used were per protocol or were clinician directed. Most studies were specific in stating that treatment methods were up to the discretion of the practitioner, whereas a few studies42,47,48 attempted to employ a specific treatment protocol. Comparators vary from SC or sham,37-40,43,45,50 pharmacologic,44 exercise or physiotherapy,41,51,52, other OMTh,46-48 and chemonucleolysis.49
Summary of OMTh Treatments and Comparator Interventions
| Author/ Year | Treatment groups | Osteopathic manipulation | Comparator | Per protocol or clinician directed therapy | Cointervention use allowed description |
|---|---|---|---|---|---|
| Albers 201837 | OMTh | Direct and indirect techniques (muscle energy, MFR, HVLA, functional techniques, and balanced ligamentous tension) and cranial/sacral techniques. | SC | Clinician directed | Pharmaceutical use NR but patients were excluded if they underwent manual therapy treatment or alternative treatment procedures during the study period. |
| Altinbilek 201841 | OMTh + Exercise | Standardized mobilization and compression for bilateral patellofemoral and tibiofemoral joints followed by a lower extremity pumping technique. These techniques are taught to the patient to apply at home as well. | Exercise consisted of quadriceps muscle strengthening exercise, leg lifting, and muscle stretching such as iliotibial band, hamstring stretching, strengthening abductor and adductor muscles of the hip. | Per protocol | No - Prevented from taking non-steroidal anti-inflammatory drugs 1 week before and during the study. Paracetamol up to 3g/daily was allowed and drugs for systemic conditions continued. |
| Burton 2000 49 | OMTh | Soft tissue stretching in combination with low amplitude passive articulatory maneuvers and high velocity thrust to the lumbar spine and buttock musculature. | Chemonucleolysis under general anesthesia, a single dose of chymopapain. | Clinician directed | No - Patients with previous manipulations on the same area were excluded. |
| Chown 200852 | OMTh | Soft tissue massage, inhibition, muscle stretching, muscle energy, high velocity thrust (varying), articulation, mobilization, exercise advice, discussion of psychosocial issues, education, nutritional/ dietary advice. | Group exercise: Problem identification, anatomy education, home stretching exercise programme, basic postural setting use of transverses, multifidus. Manipulative physiotherapy: Education/advice, joint mobilization, soft tissue mobilization, global exercise for mobility, electrotherapy, postural correction. | Clinician directed | No - Patients with manipulations such as physiotherapy, acupuncture in the previous 3 months were excluded as well as users of steroids and anticoagulants. |
| Cuccia 201043 | OMTh | MFR, joint articulation, membranous tension, muscle energy, high-velocity, low-amplitude thrust and cranial-sacral therapy. | Use of an oral appliance, physical therapy, therapies such as hot or cold packs (or both), transcutaneous electrical nerve stimulation. | Clinician directed | Yes - Non-steroidal medications, anti-inflammatory, analgesics and/or muscle relaxants were allowed when prescribed by their medical practitioner |
| Knebl 200242 | OMTh | Treatment was defined as administration of the seven-step Spencer technique which is an articular treatment involving compression, traction, and muscle energy in various planes and axes. | The 7 positions of the Spencer technique without administration of the actual corrective forces (isometric muscle contraction). | Per protocol | NR |
| Licciardone 200338 | OMTh | Combination of MFR, strain–counter strain, muscle energy, soft tissue, high-velocity–low-amplitude thrusts, and cranial–sacral. | ROM activities, light touch, and simulated OMTh techniques. | Clinician directed | Yes - Usual or other low back care allowed in both arms except OMTh or chiropractic manipulation. |
| Licciardone 201350 | OMTh | The lumbosacral, iliac, and pubic regions were targeted using high-velocity, low-amplitude thrusts; moderate velocity, moderate-amplitude thrusts; soft tissue stretching, kneading, and pressure; MFR; positional treatment of myofascial tender points; and isometric muscle activation. | Sham OMTh involved hand contact, active and passive range of motion, and techniques that simulated OMTh but used such maneuvers as light touch, improper patient positioning, purposefully misdirected movements, and diminished physician force. | Clinician directed | Yes - Patients could self-initiate LB cotreatments including prescription and non-prescription drugs, exercise programs, lumbar supports, complementary, alternative medicine and physical therapies. |
| Marske 201844 | OMTh & OMTh + Gabapentin | Treatment modalities included MFR, muscle energy, counter strain, facilitated positional release, articular ligamentous, high velocity/low amplitude, and cranial sacral OMTh. Indirect moving to direct as tolerated by the patient. | Gabapentin with variable dose (300mg to 900mg/day). | Clinician directed | Concurrent medications were continued. |
| Marti-Salvador 201848 | Diaphragm OMTh | Lumbar MFR, normalization of the iliolumbar ligament, pumping, traction to the lumbar and sacral regions, techniques directed to the diaphragm included pumping, inhibition, muscle stretching, and a global abdominal hemodynamic maneuver. | Manual contact was applied but with no therapeutic intention. | Per protocol | Yes - Cointerventions were not analyzed - a noted limitation of the study. |
| Papa 201245 | OMTh | Different techniques were used based on the results of the exam, objective techniques were performed on any body part that the osteopath found to be correlated with the disorder and the patient's functional limitation with considerations to myofascial, visceral, articulating and head structures. | Postural examination and palpation of non-specific different parts of the body in different positions supine. | Clinician directed | Yes - Patients were subjected to the usual therapy established as a result of medical specialist visits but were not reported. |
| Schwerla 200840 | OMTh | Osteopathic techniques included direct techniques (high velocity, muscle energy, MFR), indirect techniques (functional techniques, balanced ligamentous tension), visceral and/or cranial techniques. | Inert therapeutic ultrasound. | Clinician directed | Yes - Excluded patients with concomitant physical therapy, corticosteroid use, anticoagulants. Patients kept a diary of analgesic and muscle relaxant use. |
| Silva 201846 | OMTh | Osteopathic manipulation technique to the stomach followed by the liver. | Placebo manipulation technique | Per protocol | No - Patients using analgesics, muscle relaxants and anti-inflammatory drugs in the 5 days prior to the intervention were excluded. |
| Stepnik 201839 | OMTh | Osteopathic techniques employed 5 specific techniques to the anterior neck region. These included superficial fascia stretch, pretracheal fascia stretch, carotid sheath stretches, deep cervical fascia stretches, and suspensory ligament of pleural cupula stretch | Laser therapy using Polaris 2 laser (turned off) | Per protocol | NR |
| Tamer 201747 | vOMTh | Soft tissue mobilization, muscle-energy techniques, manipulation and mobilization for lumbar and thorax regions, lymphatic and liver pumping techniques, pelvic floor, diaphragm relaxation techniques, arterial, venous and neural techniques, fascial mobilization for visceral organs. | Soft-tissue mobilizations, muscle-energy techniques, manipulation and mobilization for lumbar and thorax regions. | Clinician directed | Yes - Physiotherapy used in conjunction with both treatment arms aimed at spinal stabilization strengthening and stretching. |
| Vismara 201251 | OMTh + SE | High-velocity, low-amplitude thrust in thoracic spine, cranial techniques, and MFR at the practitioner's discretion. | Active exercises, and education: reinforcing and stretching of the back muscles; self-mobilizing the spine and pelvis; posture and breathing techniques; providing patients with correct ergonomic knowledge for the safe use of the spine and information on the changes in spinal physiology, pain, and posture as related to obesity and other risk factors. | Clinician directed | NR |
Abbreviations: CCT, conventional conservative therapy; HVLA, high velocity low amplitude; MFR, myofascial release; MT, manual therapy; NR, not reported; OMTh, osteopathic manual therapy; ROM, range of motion; SC, standard care; SE, specific exercise; vOMTh, visceral osteopathic manual therapy.
Risk of Bias
A summary of the ROB is given in Table 3. None of the included studies met all criteria for ROB. Except for 2 studies,39,43 all other studies were low risk for allocation concealment and random sequence generation. Except for 7 studies,37,39,40,43,47,49,51 outcomes were assessed by an independent evaluator, whereas in 2 studies patients were blinded to manipulation.42,46
Risk of Bias in the Included Studies
| Authors | Random sequence generation | Allocation concealment | Blinding of the participants | Blinding of the healthcare provider | Blinding of the outcome assessors | Drop out > 20% |
|---|---|---|---|---|---|---|
| Albers 201837 | Low risk | Low risk | High risk | High risk | High risk | Low risk |
| Altinbilek 201841 | Low risk | Low risk | High risk | High risk | Low risk | Low risk |
| Burton 200049 | Low risk | Low risk | High risk | High risk | High risk | High risk |
| Chown 200852 | Low risk | Low risk | High risk | High risk | Low risk | High risk |
| Cuccia 201043 | High risk | High risk | High risk | High risk | High risk | High risk |
| Knebl 200242 | Low risk | Low risk | Low risk | High risk | Low risk | High risk |
| Licciardone 200338 | Low risk | Low risk | High risk | High risk | Low risk | High risk |
| Licciardone 201350 | Low risk | Low risk | High risk | High risk | Low risk | High risk |
| Marske 201844 | Low risk | Low risk | High risk | High risk | Low risk | High risk |
| Marti-Salvador 201848 | Low risk | Low risk | High risk | High risk | Low risk | Low risk |
| Papa 201245 | Low risk | Low risk | High risk | High risk | Low risk | Low risk |
| Schwerla 200840 | Low risk | Low risk | High risk | High risk | High risk | Low risk |
| Silva 201846 | Low risk | Low risk | Low risk | High risk | Low risk | Low risk |
| Stepnik 201839 | High risk | High risk | High risk | High risk | High risk | Low risk |
| Tamer 201747 | Low risk | Low risk | High risk | High risk | High risk | Low risk |
| Vismara 201251 | Low risk | Low risk | High risk | High risk | High risk | Low risk |
Pooled Analysis
Pain severity: Among the 16 studies, poolable data were available from 13 studies.37-41,43,45-48,50-52 The collective sample size from all poolable studies for pain outcomes was 996. In total, we had 3 pooled analyses based on OMTh and comparators for pain severity (Figure 2). The GRADE is reported in Table 4.
Pain outcome. (A) OMT vs. standard care, (B) vOMTh vs. gOMTh, (C) OMT + excercise vs. exercise. Abbreviations: OMT, osteopathic manipulative treatment; gOMTh, general osteopathic manipulative therapy; OMTh, osteopathic manipulative therapy; vOMTh, visceral osteopathic manipulative therapy.
GRADE Table (Quality of Evidence)
| Intervention | Number of studies and (n=) | Risk of bias | Inconsistency | Imprecision | Indirectness | Publication bias | Quality of evidence |
|---|---|---|---|---|---|---|---|
| Pain severity | |||||||
| OMTh + Exercise vs. Exercise (Moderate) | 2 (n=106) | High | Low risk | Precise | Not detected | Not detected | 0+++ |
| OMTh vs. SC (Moderate) | 6 (n=710) | High | Low risk | Precise | Not detected | Not detected | 0+++ |
| vOMTh vs. gOMTh (Moderate) | 3 (n=133) | High | Low risk | Precise | Not detected | Not detected | 0+++ |
| Disability | |||||||
| vOMTh vs. gOMTh (Moderate) | 2 (n=79) | High | Low risk | Precise | Not detected | Not detected | 0+++ |
| OMTh vs. SC (Moderate) | 2 (n=486) | High | Low risk | Precise | Not detected | Not detected | 0+++ |
| OMTh + Exercise vs. Exercise (Moderate) | 2 (n=106) | High | Low risk | Precise | Not detected | Not detected | 0+++ |
| Quality of life | |||||||
| OMTh vs. SC (Moderate) | 2 (n=120) | High | Low | Precise | Not detected | Not detected | 0+++ |
| Risk of bias among all the included studies was high, which lowers the quality of evidence. | |||||||
Abbreviations:gOMTh, general OMTh; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; OMTh, osteopathic manual therapy; SC, standard care; vOMTh, visceral OMTh.
OMTh vs. SC: Six studies37,38,40,43,45,50 with 710 patients were included in this analysis. Moderate quality evidence showed that as compared to SC, OMTh was significantly associated with pain reduction [SMD (95%CI) = -.37 (-.58, -.17)].
Visceral OMTh vs. general OMTh: Three studies46-48 with 133 patients were included in this analysis. Moderate quality evidence showed that, as compared to general OMTh [gOMTh], visceral OMTh [vOMTh] was significantly associated with pain reduction [SMD (95%CI) = −.74 (−1.09, −.39)].
OMTh plus exercise vs. exercise only: Two studies41,51 with 106 patients were included in this analysis. Moderate quality evidence showed that OMTh in combination with exercise was significantly associated with pain reduction [SMD (95% CI) =−1.25 (−1.67, −.83)].
Disability
Of the eligible 16 studies, poolable data concerning disability was available from 8 studies.39,41,47-52 The collective sample size from all poolable studies for disability outcomes was 742. There were 3 pooled analyses based on OMTh and the various comparators in total (Figure 3A-C).
OMTh vs. SC: Two studies40,50 with 486 patients were included in this analysis. Moderate quality evidence showed that, as compared with SC, OMTh was significantly associated with reduction in disability and/or function [SMD (95%CI)=−1.04 (−1.23, −.85)].
vOMTh vs. gOMTh: Two studies47,48 with 105 patients were included in this analysis. Moderate quality evidence showed that vOMTh as compared to gOMTh was significantly associated with improvement in disability (SMD (95%CI) =−.52 (−.91, −.13)].
OMTh plus exercise vs. exercise only: Two studies41,51 with 106 patients were included in this analysis. Moderate quality evidence showed that OMTh combined with exercise as compared to exercise alone was significantly associated with improvement in disability [SMD (95% CI) =−1.15 (−1.57, −.74)].
Quality of life: Of the eligible 16 studies, poolable data were available from 2 studies.37,45 The collective sample size from all poolable studies for QOL outcomes was 120. Due to the small number of studies, we had single pooled analysis (Figure 3D). Moderate quality evidence showed that OMTh was significantly associated with improved QOL as compared to SC [SMD (95% CI) =.67 (.29, 1.05)].
Disability outcomes (A) OMTh vs. standard care, (B) vOMTh vs. gOMTh, (C) OMTh + exercise vs. exercise, and (D) quality of life outcome measure, standard care vs OMTh. Abbreviations: OMT, osteopathic manipulative treatment; gOMTh, general osteopathic manipulative therapy; OMTh, osteopathic manipulative therapy; vOMTh, visceral osteopathic manipulative therapy.
For any of the pooling with FEM, the effect size did not change when reanalyzed with REM. The summary of the non-poolable studies and RTW are given in Table 5. Three studies38,49,50 showed that the effects of OMTh on pain, disability, and RTW were short term, with the effect declining by final follow up.
Outcomes of Unpoolable Studies
| Author | Number of participants analyzed | Outcome measuring scale | Conclusion ES=SMD (95% CI) | ||
|---|---|---|---|---|---|
| OMTh | Comparator | ||||
| Pain | |||||
| Burton 200049 | 15 | 15 | VAS | At the beginning of the treatments, OMTh showed significant improvement in pain severity but at 12 months follow up the effect was not significant. ES=-.07 [-.79, .64] | |
| Knebl 200242 | NR | NR | Pain rating scale (0-10) | A total of 29 subjects were randomly assigned to either a treatment (OMTh) group or a control group for 14 weeks had significantly decreased perceived pain (P<.01). | |
| Marske 201844 | 10 | 8 | WBF | OMTh + Gabapentin vs. Gabapentin: Within group difference showed that Patients receiving combination of OMTh and Gabapentin had significant improvement in the pain reduction [-2.9 (-5.6, -.3) vs. -.6 (-3.2, 2)] respectively. Between group difference showed no significant improvement between combination of OMTh and gabapentin vs. gabapentin alone. ES=-.65 [-1.61, .31] | |
| 11 | 8 | OMTh vs. Gabapentin: within group difference showed that patients receiving OMTh had significant improvement in the pain reduction as compared to the gabapentin alone [-2.4 (-4.0, -.80 vs. -.6 (-3.2, 2)] respectively. Between group difference showed no significant difference between OMTh vs. gabapentin. ES=-.64 [-1.57, 0.30] | |||
| Disability outcomes | |||||
| Burton 200049 | 15 | 15 | RDQ | At the beginning of the treatments, OMTh showed significant improvement in disability but at 12 months follow up the effect was not significant. ES=-.22 [-.93, 0.5] | |
| Chown 200852 | 39 | Group Exercise=35 Physiotherapy=24 | ODI | OMTh vs. Exercise= Within group difference showed reduction in disability for OMTh, physiotherapy and group exercises [−5.0 (−1.6 to −8.4)], [−4.1 (−1.4 to −6.9)] and [−4.5 (−.9 to −8)] respectively. Between group difference for OMTh vs. Physiotherapy and OMTh vs. group exercises were non-significant [-.09 (-.55, .37)]; [-.05 [(-.56, .46)], respectively. | |
| Licciardone 200338 | 32 | Sham=19 | RMDQ | There was improvement initially, but it declined with time. However, there were no significant changes over time among the treatment groups in the RMDQ. | |
| No intervention=15 | |||||
| Quality of Life outcome | |||||
| Chown 200852 | 28 | Group Exercise=35 | Euro-QOL | Patients in the physiotherapy group and OMTh group had a significant improvement in the QOL at 6 months [ 0.10 (.01 to .18)] and [.11 (.02 to .19)] respectively but not in group exercise [.08 (−.02 to .18)]. Between group difference showed no significant improvement in OMTh vs. physiotherapy and OMTh vs. group exercise [.04 (-.41, .50)] and [.13 (-.40, .66)] respectively. | |
| Physiotherapy= 4 | |||||
| Licciardone 200338 | 32 | 34 | SF-36- Physical component summary | OMTh was not significantly associated with improvement in physical component summary score. ES=.08 [-.40, .57] | |
| Licciardone 201350 | 230 | 225 | SF-36 - General health | OMTh was not significantly associated with improvement in overall general health. ES=0 [-.18, .18]. | |
| Schwerla 200840 | 22 | 18 | QOL, SF-36 - Bodily pain | The values of the osteopathic group showed better results for all aspects and a significant reduction for ‘bodily pain’ (P=.019). | |
| Return to Work | |||||
| Licciardone 200338 | 32 | Sham=19 | Number of lost workdays in the past 4 weeks | There were no substantial changes among the treatment for lost work or school days over time. | |
| No intervention=15 | |||||
| Licciardone 201350 | 180 | 180 | Number of lost workdays in the past 4 weeks | The OMTh participants were less likely than the sham OMTh participants to report work disability due to LBP at the week 4 and 8 mark, respectively. Neither of the groups showed significant improvements at week 12. | |
Abbreviations: ES, standard mean deviation (95% confidence interval); LBP, low back pain; NR, not reported; ODI, Oswestry Disability Index; OMTh, osteopathic manual therapy; QOL, quality of life; RDQ, Reflux Disease Questionnaire; RMDQ, Roland Morris Disability Questionnaire; SF-36, Short Form Health Survey; SMD, standardized mean difference; VAS, visual analog scale; WBF, Wong-Baker FACES Pain Rating Scale.
Return to work: Two studies38,50 explored the effectiveness of OMTh on RTW. Licciardone et al50 reported improvements in the number of days of work missed within 4 weeks. Patients in the OMTh group had significant RTW at 4 weeks, but not at 12-week follow up.
Subgroup and sensitivity analysis: We performed a sensitivity analysis that was based on LBP but ignored differences in OMTh intervention and comparators and found high heterogeneity (I2=59%; P=.0006; Figure 4A), which supports the rationale to pool according to OMTh types and comparators. Similarly, the subgroup analysis between sham and SC comparators did not show any significant differences between the two subgroups. The test of interaction (I2=61.4%; P=.11) between both groups was not significant, thus justifying our reason to pool sham and SC comparators together (Figure 4B).
Sensitivity and subgroup analysis. (A) Based on low back pain while ignoring the OMTh type and comparator type. (B) Based to compare the sham OMTh vs. standard care (pain severity). Abbreviations: OMTh, osteopathic manipulative therapy.
Discussion
Overall, our results indicate OMTh can be employed as an effective treatment approach for CNCP patients. Moderate quality evidence showed that vOMTh was significantly associated with reduction in pain severity and disability. OMTh in combination with exercise (vs. exercise only) was significantly associated with reduction in pain severity and disability. Although OMTh was not significantly associated with RTW compared to SC, it showed significant effects in reducing pain, disability, and improving QOL. When compared with other interventions such as chemonucleolysis, physiotherapy, and pharmacologic agents, OMTh did not show significant improvements in pain severity, disability, or QOL; however, the evidence regarding OMTh in comparison with chemonucleolysis, physiotherapy, and gabapentin is based on single studies.
Strengths and Limitations
The key strengths of our review were that, first, we focused on broader patient important outcomes such as reduction in pain severity, functional limitations, improvement in QOL, and RTW. Second, our search strategy was broad and up to date, and methodologically our review was very rigorous, because we reported our results clearly and transparently, allowing for more precise interpretation. Third, this is, to the best of our knowledge, the first systematic review and meta-analysis that pooled studies based on the similarity between the interventions and comparators, which acted to reduce the heterogeneity in our pooled analyses. We performed a sensitivity analysis based on LBP, ignoring the differences in OMTh and comparators as in previous reviews, and found that heterogeneity was 59% (p=.02), thus supporting our rationale to pool studies based on homogeneity of comparator.
Our review also had several limitations. First, we inherited limitations from the primary studies, such as high ROB, for which we downrated quality of evidence for major bias components such as random sequence generation and lack of blinding. Although none of the included studies in our review met all criteria of ROB, this is a common limitation to all procedure-based clinical trials, because it is nearly impossible to blind both patients and practitioner(s). Second, the eligible studies were not powered enough and dropout rate in the eligible studies was very high; except for 2 studies,48,50 no others accounted for missing data. Small sample sizes and high dropout rates increase the risk of error in interpreting the results because of over- or underestimating the effect.53,54 This was obvious in the study50 that used a large sample size and intention to treat; the results were more precise than any other study with a small sample size in pooled analyses. Third, we did not have enough studies to do subgroup analyses based on our a priori evidence as reported in the protocol, including ROB, duration of chronic pain, and frequency of OMTh; comorbid psychologic and/or medical conditions; and the use of cointerventions. Fourth, because of the nature of current evidence, we were unable to explore the effectiveness of OMTh in comparison to medical interventions in a pooled analysis44 and, because of incomplete reporting of data, many studies were unpoolable,42,49,52 particularly for RTW.38,50
Most of our findings align with previous systematic reviews28-30; however, our pooled results showed lower heterogeneity. High heterogeneity in a pooled analysis can confound the interpretation of the results55-57 and often indicates that studies are either clinically or methodologically different and should be reported descriptively.35 As with previous reviews, 28-30 the quality of evidence (GRADE assessment) in our review was moderate. Previous reviews downrated the GRADE assessment for high heterogeneity but not for high ROB. With respect to ROB, random sequence generation and blinding are considered major influencers56,57 and will lower the confidence. We downrated the quality of evidence for high ROB, but heterogeneity in our pooled analyses was low, which makes the interpretation more transparent. A few studies in our review identified the effect of OMTh as short term30,38,43,49,50; similar findings were also reported in previous studies26 and are a common occurrence with other manipulation techniques.58,59 As compared to previous reviews, our search strategy was broader, more up to date, and included studies with CNCP28-30 and RCTs27,60 only. We were also cautious about not including duplicate or substudies of the main trials, which was a limitation of a previous review.26
Clinical Implications
There was moderate quality evidence that OMTh is effective in reducing pain severity and disability and improving QOL. An interesting finding in our review was that pain symptoms improved with OMTh, although OMTh provided significant RTW at 4 weeks but not at 12-week follow up. It is important to consider that reduction in pain may not necessarily be the only contributor, because RTW also depends on the psychologic and physical demands of the individual's workplace.61 As we focused on patient-important outcomes, there is a potential that improvements in pain, disability, and QOL with OMTh will improve patient's psychosocial well-being and self-esteem, which may enhance the likelihood of RTW. This might also be considered as evidence that, because of chronicity and deconditioning associated with CNCP, more frequent and longer courses of OMTh will be helpful with the multiple aspects of involvement, because the pathophysiology becomes more complex and maintains achieved levels of musculoskeletal function.62-64 Another important finding in our review is that when vOMTh techniques were included in treatment, there was improved effectiveness as compared to gOMTh techniques in pain reduction and disability. Possible explanations for this might be a greater consideration for the anatomic and fascial connections relative to viscero-somatic reflexes potentially involved in LBP, which constitutes key osteopathic philosophy.64-66
Conclusion
This is the most comprehensive review to date, to our knowledge, done with methodologic rigor that considers the effectiveness of OMTh in CNCP. Our findings provide evidence that OMTh alone or in combination with exercise is effective in pain, disability and increasing QOL. vOMTh techniques are proven more effective than gOMTh, which does not consider visceral involvement. Due to the more complex pathophysiology involved, more frequent regular OMTh might provide better results.62-64 Our results should, however, be interpreted cautiously because of small sample sizes, high ROB, and high dropout rates. In the future, there is a need for high quality RCTs with larger sample sizes to better demonstrate the effectiveness of OMTh in the management of CNCP.
Author Contributions
Drs Rehman, Ferguson, Blair, Bozek, Alison, and Johnston provided substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; Drs Rehman, Ferguson, Blair, Bozek, Johnston drafted the article or revised it critically, provided expert advice for important intellectual content; all authors gave final approval of the version of the article to be published; and all authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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