Table 1

Characteristics of the included systematic reviews and meta-analyses

First author, year, country	Date assessed as up to date	Conditions	Trials number, participants number	Gender distribution, age (years)	Intervention (co-intervention): description. Number of treatments (SD)	Control or comparison description	Outcomes assessed	Time points reported	Main results	Definition used to measure AEs* Reported AEs	AMSTAR-2
Musculoskeletal conditions: low back pain
De Oliveira Meirelles, 2013,24 Brazil	NR	CLBP, CLBP in pregnancy, LBP with menopausal symptoms, LBP in obese, LBP with sciatica.	5 RCTs, 278 adults. 1 CLBP, 1 CLBP in pregnancy, 1 LBP with menopausal symptoms, 1 LBP in obese, 1 LBP with sciatica.	Gender:85% female,15% male. Mean age 40 (from 4 RCTs).	OMT (UOBC, SE): OCF, ART, HVLA, MRT, MET, range of motion technique. Treatments: median 10 (7-10)‡	SUT, NT, SM, chemonucleolysis.	Pain: VAS, dichotomous pain, pain scale.	Treatment time: 12 weeks and 15 weeks (from 2 RCTs). Evaluation: 1, 3 and 6 months (from 1 RCT).	OMT improved LBP in comparison with no intervention (but not with SM).	NR	Critically low
Franke, 2014,25 Australia	NR	ANSLBP, CNSLBP, NSLBP in pregnancy, NSLBP in PP.	15 RCTs, 1502 adults. 10 NSLBP, 3 NSLBP in pregnancy, 2 NSLBP in PP.	Gender: NR. Mean age 36 (from 13 RCTs).	OMT (UC, heat and PT, UOBC, SE): NR. Treatments: median 4 (4–6)‡	SUT, NT, SM, UC, PT, SWD.	Pain: VAS, NRS, MGPQ. Functional status: RMDQ, OPQ, ODI, LBP_DQ, Kinematic of thoracic/lumbar spine /pelvis during forward flexion, QBPDS.	Period: 2–9 weeks, 1–3- 6 months.	OMT was effective in pain and functional status in ANSLBP, CNSLBP, NSLBP in pregnant and NSLBP in PP.	NR Only 4 RCTs reported AEs. 2 RCTs reported minor AEs such as stiffness and tiredness; 1 RCT reported that 6% of patients had AEs (but not serious). 1 RCT reported that no AEs occurred.	Low
Franke, 2017,26 Australia	NR	ANSLBP, CNSLBP and /or pelvic pain during pregnancy and PP.	8 RCTs, 850 adults. 5 LBP in pregnancy, 3 LBP in PP.	Gender: 100% female, Mean age 29.5	OMT (UOBC): NR. Treatments: Pregnancy median 7 (5.5–7). Postpartum median 4 (4–4.5)‡	SUT, NT, UC.	Pain: VAS, QVAS, FP. Functional status: RMDQ, QPP, QBPDS, PGPQ, OPQ.	Pregnancy: ranging from 3 to 9 weeks; follow-up 1 and 2 weeks. Postpartum: 6 weeks. Follow-up 2 weeks.	OMT significantly improved pain functional status in women with LBP during pregnancy and PP.	NR No serious AEs (from 3 RCTs†). 1 RCT reported occasional tiredness in some patients.	Low
Dal Farra, 2020,27 Italy	Inception to April 2020	CNSLBP	6 RCTs¶,739 adults.	Gender: NPTC Mean age 46 (from 4 RCTs), median age 41 (29-51)‡	OMT (SE, UC): HVLA, MET, CST, MFR, MVMA. Treatments: range 5–10 sessions, median 6 (5-8)‡	SM, PT, SE.	Pain: VAS. Functional status: RMDQ, ODI, SF-36, EQ-5D, BDI.	Ranging from 2 weeks to 6 months. Follow-up: from 1 month to 1 year.	OMT significantly improved pain and functional status in CNSLBP in the short-term (but not in the long-term).	Frequency of adverse events and/or relative study withdrawals, and self-reported scales and questionnaires including quality of life and psychological function (eg, fear avoidance beliefs, catastrophising, pain-related fear); additional indicators considered were frequency of analgesic and/or NSAIDs use, economic impact or cost reduction and patient’s care satisfaction. No AEs (from 5 RCTs). 1 RCT reported increased back muscle spasticity in a patient.	Low
Musculoskeletal conditions: neck pain
Franke, 2015,28 Australia	NR	CNSNP	3 RCTs, 123 adults.	Gender: NR. Mean age 44.	OMT (SUT, UC): NR. Treatments: median 5 (5-6)‡	SM, PT.	Pain: VAS, NRS, NPPQ. Functional status: NDI, NQ.	Ranging from 6 to 11 weeks. Follow-up: 3 months (in 2 RCTs).	OMT significantly improved pain, but not functional status in CNSNP.	NR Only 1 RCT reported not serious AEs, such as tiredness on the day of treatment and short-term aggravation of symptoms in other ‘familiar’ regions, were noted.	Low
Musculoskeletal conditions: chronic non-cancer pain
Rehman 2020,29 Canada	NR starting date. Until July 2019	CNCP: Fibromyalgia, TMD, CNSLBP, CNSBP, CNSNP, CNP.	7 RCTs**, 759 adults. 1 Fibromyalgia, 1 TMD, 1 NSNP, 1 CNSBP, 2 CNSLBP, 1 CNSNP.	Gender: 60% female, 40% male. Mean age 52 (from 5 RCTs), range 23–54 (from 2 RCTs).	OMT (non-steroidal medications, anti-inflammatory, analgesics and/or muscle relaxants, UC, SE, lumbar supports, physical therapies and CAM): MET, MFR, HVLA, BLT, CST, JA, MT, ST, FPR. Treatments: NR.	SUT, SE, PT, SC, use of an oral appliance, hot and/or cold packs, TENS, SM, LT, ROM activities, LTP.	Pain: VAS. Disability: RMDQ. SF-36, QOL	Duration of trial or follow-up period: ranging from 42 to 168 days (1–6 months).	OMT, in comparison to SC, was significantly effective in reducing pain and increasing disability as well as in improving QoL.	NR	Low
Paediatric conditions
Posadzki, 2013,30 South Korea	Inception to November 2012	Paediatric conditions: CP, respiratory conditions, OM, musculoskeletal function, ADHD, prematurity, IC, CNLDO, DV.	17 RCTs, 887 neonates/infants (from 16 RCTs)§. 2 CP, 4 respiratory conditions, 3 OM, 3 musculoskeletal function, 1 ADHD, 1 prematurity, 1 IC, 1 CNLDO, 1 DV.	Gender: NR. Range from premature infants>28 weeks to 18 years.	OMT: VO, CST, OMT techniques (ART, BLT, BLM, CS, FPR, MET, MFR or rib-raising). Treatment: median 4 (3-5)‡	UC, NT, SM, WL, SM +placebo, SM +Echinacea, postural drainage, bronchodilators.	Cerebral palsy: CHQ, GMFM-66, PEDI, WeeFIM. Respiratory: RR, EV, flow, MEP, PEF. Musculoskeletal: TM, SF, Kinesiographics (MO, MOV, MCV, OVA, CVA). Preterm infants: LOS, DWG. ADHD: Conners Scale. Infantile colic: MNHSCS. Otitis media: Antibiotic use, tympanograms, Audiometrics, SI, surgery -free months, reflectometer. CNLDO: FDT, MJT. Dysfunctional voiding: DV symptoms.	Cerebral Palsy: 6 months follow-up. Respiratory, Musculoskeletal, ADHD, congenital nasolacrimal duct obstruction, dysfunctional voiding: posttreatment. Prematurity: discharge from hospital.	No conclusive evidence on the efficacy of OMT for any paediatric condition due to i) low methodological quality of RCTs (when conditions were evaluated by individual RCTs) and ii) contradictory results for the conditions under which two RCTs were performed.	NR AEs not evaluated in 11 RCTs. No AEs occurred in 4 RCTs. 1 RCT reported patients (4) aggravation of vegetative symptoms after OMT. 1 RCT reported AEs not related to OMT.	Critically low
Neurological conditions
Cerritelli 2017,31 Italy	Inception to April 2016	Primary headache: migraine, tension-type headache.	5 RCTs, 235 adults. 2 migraine, 3 tension-type headache.	Gender: 78% female, 22% male (from 3 RCTs). Mean age 39.4 (from 3 RCTs).	OMT (UC, triptans, PMR): NBT (in three studies), use of protocols (in two studies). Treatment: median 4 (3-5)‡	UC, SM, OE, PMR, rest.	HIT-6 score, HF, WD, PI, DC.	Ranging from IAT to 6 months. Follow-up: 1, 3 months.	OMT reduced pain intensity, frequency and disability in patients with headache.	Number and types of AEs. AEs not evaluated in 3 RCTs, 2 RCTs reported no AEs.	Low
Visceral conditions
Muller 2014,32 Australia	Inception to October 2013	Irritable bowel syndrome	5 RCTs. 204 adults.	Gender: 79% female, 21% male (from 3 RCTs). Mean age 47.	OMT: applied to different body region, VO (approach on the abdomen and spine, abdomen and sacrum), NBT. Treatments: median 5 (3-5)‡	UC, SM.	Pain: VAS. Constipation, diarrhoea, AD, RS, CTT, meteorism. IBS severity score, FIS score, HAD, BDI, IBSQoL2000, FBDSI.	Ranging from 1 week to 3 months. Follow-up: short-term (2, 4 weeks), long-term (3, 12 months).	OMT, in comparison to sham therapy or standard care, reduced the symptoms of IBS, such as abdominal pain, constipation, diarrhoea, and improved general well-being.	NR All RCTs reported that no serious or statistically significant AEs occurred.	Low

*Reported by the Authors of the SRs.
†In personal communications from authors of two RCTs.
‡Median (Q1–Q3).
§The number is not reported for a RCT on asthma.
¶Subgroup analysis.
**16 RCTs, only seven trials were used in our study.
IBSQoL 2000, IBS quality of life; AD, abdominal distension; ADHD, attention deficit /hyperactivity disorder; AE, adverse events; ANSLBP, acute non-specific low back pain; ART, articulatory treatment; BDI, Beck Depression Index; BLM, balanced membranous tension; BLT, balanced ligamentous tension; CHQ, child health questionnaire; CNCP, chronic non-cancer pain; CNLDO, congenital nasolacrimal duct obstruction; CNP, chronic neck pain; CNSBP, chronic non-specific body pain; CNSLBP, chronic nonspecific low back pain; CNSNP, chronic nonspecific neck pain; CP, cerebral palsy; CS, counterstains; CST, cranial sacral therapy; CTT, colonic transit time; CV4, a technique in cranial field; CVA, cranial vault asymmetry; DC, drug consumption; DV, dysfunctional voiding; DWG, daily weight gain; EV, expiratory volume; FBDSI, functional bowel disorder severity Index; FDT, fluorescein disappearance test; FIS, fatigue impact scale; FP, frequency of pain; FPR, facilitated positional release; GMFM-66, gross motor function measure-66; HAD, hospital anxiety and depression; HF, headache frequency; HIT-6, headache impact test-6; HVLA, high velocity low amplitude thrust; IAT, immediately after treatment; IBS, irritable bowel syndrome; IC, infantile colic; JA, joint articulation; LBP, low back pain; LBP-DQ, low back pain disability questionnaire; LOS, length of stay; LT, light touch; LTP, laser therapy; MCV, maximal closing velocity; MEP, mid expiratory phase; MET, muscle energy treatment; MFR, myofascial release; MGPD, Mc Gill pain questionnaire; MJT, modified jones test; MNHSCS, mean numbers of hours spent crying and sleeping; MO, maximal mouth opening; MOV, maximal opening velocity; MRT, myofascial release treatment; MT, membranous tension; MVMA, medium velocity medium amplitude; NBT, need based treatment; NDI, Neck Disability Index; NP, not performed; NPPQ, Northwick park pain questionnaire; NPTC, not possible to calculate; NQ, Nordic questionnaire; NR, not reported; NRS, numeric rating scale; NSNP, non-specific neck pain; NT, no treatment; OCF, osteopathy in cranial field; ODI, oswestry disability Index; OE, osteopathic evaluation; OM, otitis media; OMT, osteopathic manipulative treatment; OPQ, oswestry pain questionnaire; Pedi, paediatric evaluation of disability inventory; PEF, peak expiratory flow; PGPQ, pelvic girdle pain questionnaire; PI, pain intensity; PMR, progressive muscular relaxation exercise; PP, postpartum; PT, physical therapy; QBPDS, Quebec back pain disability scale; QPP, questionnaire postpartum; QVAS, quadruple visual analogue scale; RMDQ, Roland Morris disability questionnaire; ROM, range of movement; RR, respiratory rate; RS, rectal sensitivity; SC, standard care; SD, standard deviation; SE, specific exercise; SF, spine flexibility; SI, surgical intervention; SM, sham manipulation; ST, Spencer technique; SUT, sham ultrasound treatment; SWD, short-wave diathermy; TENS, transcutaneous electrical nerve stimulation; TM, Trunk morphology; TMD, temporomandibular disorder; UC, usual care; UOBC, usual obstetrical care; VAS, visual analogic scale; VO, visceral osteopathy; WD, work disability; WeeFIM, functional independence measure for children; WL, waiting list.