Muscle cramps lead to continuous, involuntary, painful, and localised contractions of a whole muscle faction, a single muscle, or selected muscle fibres. In healthy persons or the presence of diseases, cramps might endure from seconds to a minute for idiopathic or recognised reasons. The palpation of the cramped muscle region reveals a knot [12].

Early mobilisation induces an increase in local vascularity in the lesion area, better regeneration of muscle fibres, and better parallel orientation of regenerated myofibrils concerning movement restrictions [13]. However, re-injury at the initial site of trauma is common if active mobilisation is started immediately after injury [14].

Muscle fatigue is one of the main factors in decreasing muscle flexibility [15]. Numerous ways have been used over time to facilitate muscle recovery from fatigue, such as stretching techniques [16], massages, active recovery [17], contrast water therapy [18], cryotherapy [19], and thermotherapy [20].

This review aims to highlight the multitude of physiotherapy procedures in treating muscle diseases in athletes and non-athletes. Due to the produced effects, manual therapy combined with HILT or TECAR therapy, or even all three therapies used in a treatment plan, can provide optimal muscle recovery in a shorter time; therefore, the use of combined and not isolated recovery procedures is a better alternative in muscle recovery.

Moreover, we aim to reintroduce manual therapy, a relatively old technique used in physical therapy, and to use it as an adjunct technique in the therapy of muscle conditions, along with new techniques used in physical therapy, such as HILT and especially TECAR therapy. Therefore, another purpose of this review is to combine the old techniques of physical therapy with the new ones to find a treatment plan that is as effective as possible in treating muscle diseases.

The novelty of this review consists of the association of these recovery procedures, specifically the association of manual therapy with HILT and TECAR therapy, which are usually used in isolation in the recovery process for the therapy of muscle diseases. TECAR therapy, in particular, produces many beneficial effects on the body and muscle tissue. As a result of the probes used in the treatment, we can obtain perfect collaboration with manual therapy techniques, such as passive mobilisations, massages, or manipulation.

#### **2. Materials and Methods**

The current literature review was developed between December 2021 and April 2022 utilising the PubMed, Scopus, and Web of Science databases in accordance with the PRISMA criteria. The search formula had the following form:

The records identified from the databases using the key phrases described above were created using the reference management program EndNote (X9.3.3), and the duplicate articles were also deleted with its assistance.

After that, depending on the design of the studies, we aimed to include all articles of the following type: systematic reviews, meta-analyses, case-control studies, cross-sectional studies, literature reviews, and case reports, and we excluded expert opinions, letters to the editor, and conference reports.

A word form was used to extract the data. From each article that was selected and included for review, we extracted the information that we thought fit, according to each sub-chapter, to elaborate the present literature review.

The initial search identified 341 titles in the databases described above, of which 56 duplicate articles were automatically removed, and 2 were added from other sources. The remaining 343 articles were analysed by their titles and abstracts for relevance, resulting in another 70 studies being removed. Studies were excluded at the screening stage due to items that did not fit the themes developed in all subchapters of the study (*n* = 70) because the articles dealt exclusively with orthopaedics (*n* = 34). A total of 29 articles were excluded because the articles had only the abstract visible, and 17 articles exclusively treated other muscle disorder treatment techniques/disorders. The inclusion phase resulted in 137 articles included in the study. Figure 1 represents the complete PRISMA diagram.

**Figure 1.** Study selection flowchart based on PRISMA criteria.

#### **3. Manual Therapy vs. TECAR vs. HILT Therapy**

Manual treatment is applied in treating muscle disorders in approximately every recovery program. Its effectiveness is debated, requiring much faster and more efficient recovery methods. Capacitive and resistive electrical transfer (TECAR), a type of diathermy, has recently been created as a form of deep thermotherapy and is used in sports medicine [21]. This device provides radio frequency energy, passing between an active and an inactive electrode and generating heat inside the body [22]. This therapy has shown that TECAR therapy is more efficient than a warm packet at increasing blood circulation, a conventional form of thermotherapy commonly used in clinical practice. Improving blood circulation plays an essential role in improving muscle recovery after fatigue. Thus, TECAR therapy can effectively improve muscle recovery after fatigue, which leads to maintaining and improving muscle flexibility [21].

Although manual therapy has been used to treat various muscle ailments since ancient times, for better and faster recovery of these ailments, more muscular stimulation is needed to have the desired effect (Figure 1). TECAR therapy combines manual therapy with deep thermotherapy, based on high-frequency electric currents, allowing for faster recovery of the affected muscles [23]. Due to the positive effects on muscle tissue, TECAR therapy seems to be a more helpful alternative in treating muscle disorders than conventional manual therapy, where cellular metabolism is not as strongly stimulated, and vasodilation is not as intense [24].

Laser treatment is a pain-free, non-invasive therapy that can be used to treat various clinical conditions. Laser therapy has significantly reduced acute and chronic pain, rheumatoid arthritis, chronic osteoarthritis, carpal tunnel syndrome, fibromyalgia, knee injuries, shoulder pain, and postoperative pain [25,26]. The reduction in pain after laser treatment results from its anti-inflammatory effects, the increased microcirculation and stimulation of immune processes, nerve regeneration, and the secretion of β-endorphins [26]. These properties of high-frequency laser therapy can influence the healing and regeneration of muscle tissue, which is recommended in most muscle conditions, both in athletes and non-athletes. Compared to TECAR therapy, HILT requires a much shorter treatment period, but its use with manual therapy does not seem as effective as using manual therapy with TECAR therapy because, as mentioned, the duration of treatment is short. The device does not allow a massage to be performed on the treated area. However, manipulations, massages, active or passive mobilisations, or other manual therapy techniques may be performed before or after HILT treatment (Figure 2).

**Figure 2.** The acceleration mechanism of manual therapy, TECAR therapy, and HILT.

#### **4. The Benefits of Manual Therapy in the Treatment of Muscle Diseases**

Manual therapy is a technique used in physical therapy that involves using the hands to apply a force for therapeutic purposes. Manual therapy includes a wide range of therapeutic procedures such as massages, joint mobilisations/manipulations, myofascial releases, nerve manipulations, counter-stress, and acupressure (Figure 3).

Although manual therapy can be considered today as an old technique used by physical therapists, it remains one of the basic techniques of recovery used by physiotherapists in most recovery programs [27–29].

Manual therapy has been used to treat individuals suffering from various diseases since ancient times. The use of hands for healing dates back to the Old Testament and appears to have been advocated in the fifth century B.C. Hippocrates suggested the application of manual therapy, including traction prone to associated manipulation of the spine. He proved the efficiency of several manual approaches and proposed modifications to force delivery characteristics such as direction, pace, and frequency [30] (Figure 4).

**Figure 3.** Manual therapy after Achilles tendinopathy.

**Figure 4.** Relaxing massage of the thigh muscles (quadriceps).

Currently, manual treatment is applied in treating patients with various conditions, including musculoskeletal disorders, joint dysfunctions, spinal disorders, lymphedema, musculotendinous junction disorders, cystic fibrosis, and, most importantly, after immobilisation [31].

Among the essential benefits of manual therapy are modulating pain, increasing joint mobility, especially in stiff joints and increasing range of motion, accelerating tissue repair, improving tissue stability and extensibility, reducing soft tissue inflammation, reducing muscle tension, inducing relaxation, facilitating movement, and preparing segments for exercise therapy [32]

#### **5. The Benefits of HILT Therapy in the Treatment of Muscle Disorders**

As previously stated, laser treatment is a non-invasive treatment with minimal risk of adverse effects [33].

High-intensity laser treatment (HILT) is primarily employed in physio-kinetic therapy therapeutic regimens [34–36]. The primary distinction between HILT therapy and lowintensity laser therapy is that more giant beams (power > 500 mW) are irradiated to penetrate deeper, bringing a desired large amount of multidirectional energy into the deep tissues in a short time [37,38].

Moreover, the application techniques, the treatment time, and the cost of the device are different between these two generations of laser therapy [39,40]. However, High-Intensity Laser Therapy seems to have multiple benefits in the therapy of musculoskeletal disorders, precisely due to the effects produced in the tissues and also due to the reduction in recovery time [41–43].

HILT provides high tissue energy, and its optical energy forms dynamic vibrations. It then generates photochemical effects, such as increased mitochondrial oxidation, and it facilitates the formation of adenosine triphosphate (ATP) and ultimately leads to the rapid absorption of oedema and the elimination of exudates by increasing metabolism and blood circulation [44,45].

HILT has its own photomechanical, photothermal, and photochemical properties and has many therapeutic effects, including oedema reduction, analgesic effects, and physical stimulation [46]. Another benefit of HILT is its greater penetration strength and depth into deep tissues [47].

High-intensity laser treatment (HILT) has lately been applied in fundamental research and clinical rehabilitation practice with promising results (Watt-level performance) (highintensity laser, Class IV laser) [48,49].

The high-intensity laser is usually used in two ways—pulsed and continuous [50]. Each mode impacts the tissue differently and triggers different therapeutic effects. The general therapeutic effects are bio-stimulation, pain relief, anti-inflammatory effects, superficial thermal effects, and muscle relaxation [51].

The high-intensity laser delivers energy to the cells, stimulates cellular metabolism, and promotes quicker resorption of the pro-inflammatory mediators [52].

Decreasing the concentration of pro-inflammatory mediators improves capillary permeability, resulting in the total eradication of inflammation and a speedier return to daily activities and sports. The high-intensity laser can provide extremely brief heartbeats at a maximum repetition rate [53]. This property can create real pressure. Pressure waves are transported through the tissue, stimulating the free nerve endings. According to the pain control mechanism, the mechanical stimulation of free nerve terminals causes their inhibition and, as a result, pain reduction [54]. The high-intensity laser has an immediate and long-lasting analgesic effect. The energy transferred by the continuous emission of HILT to the tissue causes superficial hyperthermia and vasodilation in the treated area [55]. As the blood perfusion increases, more blood passes through the treated area, and the muscles relax. In painful indications related to muscles, such as muscle injuries and muscle contracture, the patient feels immediate relief from discomfort triggered by muscle tension, and an amplitude of movement increases immediately [56].

Bio-stimulation means stimulating the body to help enhance healing and recovery at the cellular level. Mitochondria in cells metabolise oxygen. A cascade of respiratory enzymes processes oxygen and delivers it to ATP synthase, which synthesises the body's energy source—ATP. As a result of the quicker exchange of oxygen and metabolites caused by laser irradiation, more oxygen atoms reach the mitochondria. Mitochondria are further stimulated to synthesise ATP faster. ATP allows faster R.N.A. and D.N.A. synthesis and leads to faster recovery, faster healing, and reduced oedema in the treated area [57].

Class IV laser therapy (High-Intensity Laser Therapy) can be used to treat a range of ailments, including knee, hip, and ankle osteoarthritis; rheumatoid arthritis; shoulder pain impact syndromes [58]; hip or shoulder bursitis; lumbar disc degeneration; herniated disc sciatica; tendonitis; lateral and medial epicondylitis; plantar fasciitis; and a variety of muscle disorders [59]. Compared to other procedures used in medical recovery, high-frequency laser therapy has a limited range of contraindications, but they must be considered before starting therapy using this type of laser [60].

Pregnancy is one of the absolute contraindications of HILT therapy, and although, to date, there are no documents indicating that laser therapy is harmful to a pregnant woman or her child, to be safe and to prevent any problems, the use of this procedure in pregnancy is not recommended [61].

Another contraindication to HILT is cancer. Therefore, the use of laser therapy in a patient who has cancer or is suspected of having cancer is not recommended.

There are several relative contraindications, which each physiotherapist takes into account in the use of HILT therapy, including:

#### **6. The Benefits of TECAR Therapy in the Treatment of Muscle Diseases**

TECAR treatment is a type of non-invasive electrothermal treatment classified as deep thermotherapy, based on the planning of electric tides in the field of radiofrequency, constituting a monopolar capacitive resistive radiofrequency of 448 kHz [65–68].

TECAR or capacitive-resistive electric transfer (CRet) is often used in the treatment of muscle, joint, and tendon injuries in traumatology and sports [67,69,70]. CRet is a non-invasive electrothermal treatment characterised as deep thermotherapy based on the application of electric flows in the radiofrequency range of 300 kHz to 1.2 MHz [71–73]. Unlike superficial thermotherapy, which has a relatively limited ability to penetrate muscle tissue [74,75], CRet may create heat in deep muscle tissue, hence increasing haemoglobin saturation [76]. Applying an electromagnetic field of around 0.5 MHz to the human body is responsible for this form of therapy's physiological effects. It has been discovered that an increase in blood perfusion is associated with a rise in body temperature, and other effects, such as cell proliferation, seem to be primarily connected to the current flow [77,78]. It has been demonstrated that cell growth begins at 0.00005 A per square millimetre [69,78].

TECAR therapy is characterised by its quick action and is employed in high-performance sports because it speeds up the recovery process [79,80]. Thermal changes in the neuromotor arrangement caused by TECAR treatment generate vasodilation, minimise muscle spasms, speed up cellular metabolism, and increase the extensibility of soft tissues [81,82].

TECAR therapy is available in capacitive (C.A.P.) and resistive (R.E.S.) modes. These modes are often given with a number of immaculate medical steel probes (electrodes) that have been manufactured [83]. According to TECAR, depending on the strength of the treated tissue, the two treatment techniques generate various tissue responses. When a cushioning ceramic coating functions as a dielectric mechanism (C.A.P.) on the active electrode, energy transfer generates only heat to the superficial layers of tissue, with selective action on soft tissues with low impedance (rich in water), e.g., adipose matter, muscles, and the lymphatic system [79].

The resistive mode targets denser tissues with more fat and fibre (such as bones, ligaments, and tendons). High-frequency waves penetrate deep into tissues and cause a rise in exchange and temperature, and recent studies have shown the effects of radiofrequency on skin microcirculation and intramuscular blood flow [84,85] (Figure 5).

It should be noted that this new technology is a valuable tool in the therapy of different pathologies compared to other therapies used in recovery in terms of the presence and/or absence of specific positive effects while having distinctive features compared to conventional treatments [86]. It is guaranteed that TECAR therapy provides a balance between the therapist's manual capacity and the unique energy that this technology emanates from the tissues, thus giving therapists and patients much more satisfactory results [87]. Among its positive effects is better blood circulation, which removes inflammatory catabolites [88]. TECAR therapy also substantially improves blood circulation in the peritendinous region and increases haemoglobin saturation [89]. In addition, this therapy warms deep tissues, stimulates vascularity, promotes the repose of tissues (particularly muscle tissue), and

stimulates drainage (oedema and hematoma) [90]. Based on these properties, TECAR treatment is employed in most orthopaedic pathologies before the start of rehabilitation exercises [91].

**Figure 5.** TECAR therapy in the treatment of hamstring muscles.

Among the physiological effects of TECAR therapy are increased extensibility of collagen tissue due to reduced viscosity; reduced discomfort because of anti-irritant behaviour or release of endorphins; reduced spasms and muscle contractions due to reduced activity of secondary efferents; faster dissociation of oxygen because of more available haemoglobin [92], accompanied by a reduction in the activation energy of important chemical and metabolic reactions; vasodilation with increased local blood flow, contributing to the replenishment of oxygen and nutrients; the elimination of catabolites; and accelerated reabsorption of hemorrhagic masses [93].

#### **7. Manual Therapy–TECAR–HILT Therapy: Recommendations in the Treatment of Muscle Diseases**

Capacitive-resistive electrical transfer therapy (TECAR) is mainly used to treat musculoskeletal injuries [93]. TECAR is a deep thermotherapy non-invasive electrothermal therapy. It uses electric currents at radio frequencies ranging from 300 kHz to 1.2 MHz [90]. This current can induce warming of deep muscle tissue, improving haemoglobin saturation, increasing deep and superficial blood flow, vasodilation, increased temperature, fluid removal, and cell proliferation [94]. Responses such as increased blood perfusion appear to be associated with increased temperature, which is generated due to a physical reaction generated by current flow (Joule effect) [95]. Increased cell escalation, nevertheless, seems to be associated with the current flow rather than increased temperature. Precisely due to these effects produced by TECAR therapy, it seems ideal for treating all muscle disorders compared to other therapies used, especially in athletes [96].

As mentioned above, TECAR therapy offers two different modes of treatment: capacitive and resistive. Different therapy methods trigger various tissue reactions relying on the treated tissue's strength [92]. A ceramic layer insulates the capacitive mode, and energy transfer creates heat in the surface tissue layer's selective action in the tissues with low impedance (rich in water). The resistive mode does not have an insulating ceramic layer; the radio frequency energy travels immediately across the physique in the orientation of the unemployed electrode, causing heat to be generated in the more profound and more resilient tissues (through lower water content) [97,98]. Given the benefits induced in part by each electrode (capacitive and resistive), the capacitive mode seems ideal in the therapy of

muscle injuries, muscle cramps, spasms, contractions, and myalgias, as well as for reducing post-exercise muscle tension.

Unlike surface thermotherapy, which has a minimal ability to reach muscle tissue, TECAR therapy can generate heat in deep muscle tissue, improving haemoglobin saturation [99]. The physiological effects of this sort of therapy are caused by exposing the human body to an electromagnetic field of around 0.5 MHz. This approach has improved blood circulation, deep and surface temperatures, vasodilation, lymphatic effects, and increased cell proliferation [100]. An increase in blood strain has been noticed and is related to rising temperatures, but other effects—such as cell proliferation—seem to be mainly related to the stream of the current [101].

The mechanism of action of HILT Is not precise. It is considered to have both photochemical and photothermal effects, resulting in an anti-inflammatory, anti-edematous, analgesic, and repairing treatment. It is suspected that the analgesic influences of HILT are based on various mechanisms of action, such as slowing down the transmission of pain stimuli and increasing the production of morphine-mimetic substances in the body [102].

This treatment provides changes in blood flow and an expansion in the permeability of blood vessels and accelerates the response of cellular metabolism [103]. Furthermore, the photochemical consequences of HILT can promote collagen formation in the structure of tendons as well as enhance bloodstream and vascular resistance permeability, causing anti-inflammatory effects [104]. Thus, HILT can support the maintenance of the destroyed tissue and eliminate painful stimuli. Regarding muscle disorders, HILT is recommended in their treatment precisely because of the effects produced, initially to relieve pain and accelerate the healing process of affected muscle tissue [105].

Manual therapy appears to have been utilised in the treatment of muscle ailments since ancient times, with physio-kinetic therapists using it from the acute stages of the disease before thermotherapy and electrotherapy became widespread [106]. The manipulation of muscle tissue primarily helps to increase elasticity and prevent muscle atrophy and joint stiffness caused by trauma [107,108]. However, massages, especially in the severe phase of muscle injuries, are recommended and have many beneficial effects in the therapy of muscle contractures [109]. Passive, active, passive–active, and active–passive mobilisations are among the most used manual therapy techniques in the therapy of muscle diseases, being included in the protocol for the use of muscle diseases [110]. These techniques must be launched as quickly as necessary because, with their help, we can prevent the installation of joint stiffness and deficits [111] (Figure 6).

**Figure 6.** The advantages of recommending manual therapy, TECAR, and HILT therapy.

#### **8. Manual Therapy–TECAR–HILT Therapy: Methods of Use in the Treatment of Muscle Diseases**

Skeletal muscles allow people to move and perform daily activities. They play a crucial role in respiratory mechanics and help maintain posture and balance. They also protect vital organs in the body [112].

Various medical conditions result from abnormal skeletal muscle function [113]; these conditions include myopathies, paralysis, myasthenia gravis, urinary and/or intestinal incontinence, ataxia, weakness, tremors, and other disorders [114]. Nerve diseases can cause neuropathy and skeletal muscle dysfunction. Furthermore, skeletal muscle/tendon ruptures can occur acutely in high-level athletes or recreational sport participants and can cause a significant disability in all patients, regardless of activity status [115,116].

TECAR therapy is one of the most beneficial treatments used in muscle diseases due to the multitude of positive effects it brings to muscle tissue [117] (Figure 7).

**Figure 7.** TECAR therapy with massaging calf muscles.

Moreover, TECAR therapy has several uses for the better healing of muscle tissue. One of these is the one used by TECAR Winback therapy, where the positive electrode consists of a bracelet that the therapist places around his or her radio-carpal joint, using his or her hand to perform the treatment. This function offers the therapist better manipulation of the muscle tissue, working passively with the patient to mobilise the joint and simultaneously combining manual therapy with TECAR therapy. TECAR therapy also has fixed applicators, which are fixed in the patient in the proximity of the disease, thus offering the therapist the possibility of performing a complex treatment, combining the advantageous influences of diathermy with manual therapy and passive therapy mobilisations.

HILT (High-Intensity Laser Therapy) is a convenient, non-invasive, and painless way that improves joint mobility [118], stimulates adequate tissue deepening [119], and offers anti-inflammatory, analgesic, and other valuable benefits in tissue healing [120]. In addition, the anti-inflammatory, anti-edematous, and analgesic effects are practical in the first treatment sessions [121]. Treatment sessions are short and recommended to be conducted daily for a faster effect. Depending on the brand of laser used, HILT can be used both in direct contact with the skin and at a distance of a few millimetres from it. The patient feels a warm sensation in the treated region, which is easily tolerated.

Another benefit of HILT, for which its use is recommended, is given by the depth at which the laser penetrates the tissue, having the ability to penetrate superficial tissues, reaching the site of the lesion to be treated [122–124].

HILT is a therapy used in isolation and in combination with other thermotherapy and electrotherapy procedures [125,126]. Moreover, in most cases, it is used in conjunction with physical therapy, playing an essential role in modulating pain [127].

Manual therapy is used in all muscle diseases, isolation, and other procedures, especially in physiotherapy [128,129]. Its method of use varies, and the physiotherapist can use his or her own hands to treat various devices/accessories specific to physical therapy. Massaging is very effective in muscle contractions, fatigue, or muscle loads [130] combined with cryotherapy. Physiotherapists also use joint mobilisation during physical therapy sessions to maintain joint mobility and to make the patient aware of the movement, especially after surgery [131].

Manual resistance physical exercises performed by the physiotherapist are also practical, especially in the early stages of recovery from muscle disorders, before the patient can perform exercises with elastic or mechanical resistance.

#### **9. Manual Therapy–TECAR–HILT Therapy: Contraindications**

Although TECAR therapy currently seems to be one of the most beneficial therapies used in recovery [132], it also has several contraindications that the therapist must consider before starting treatment with this type of therapy [133]. Among the most critical absolute contraindications of TECAR therapy are patients with pacemakers, patients with hemorrhagic gastrointestinal ulcers, patients with infusion pumps and electric cable implants, patients in the first six months of pregnancy, in the treatment of localised cancerous area/tumours, patients with allergic reactions to certain substances in the conductive cream, patients with deep-vein thrombosis, patients with uncontrolled ischemic heart disease, patients with local pulmonary embolism, patients with phlebitis, and for treating areas with bleeding or where the skin has partial or open wounds (Figure 7).

In addition to the contraindications of TECAR therapy, there are several precautions that the therapist must take into account when using this type of therapy. One of them is removing metallic materials from the patient, such as bracelets, earrings, and watches, especially from the area where the treatment is to be performed. It is also good to know that TECAR therapy is recommended for adults, as it can have adverse effects on growth cartilage, although this has not yet been demonstrated [134].

HILT also has several significant contraindications that physicians and physiotherapists should consider before recommending or performing a high-intensity laser treatment. As with TECAR therapy, pregnancy is a contraindication to high-intensity laser treatment, and although there is no evidence that laser therapy can harm the pregnant woman or the child, for safety reasons, this type of treatment is recommended in the case of pregnancy [135]. Cancer is also a contraindication in the case of HILT therapy, as it is in the case of other therapies, because the effects it can have on cancer cells are not known [136]. In some countries, however, such as France, the laser is used to treat mucosal pain (Figure 8).

Unlike other therapies, HILT is also recommended for patients with pacemakers, implants, screws and plaques and even for children [137].

Manual therapy a procedure with some of the fewest contraindications, and it can be used in almost any category of patient (Figure 8). However, it is recommended to avoid using it in patients with uncontrolled hypertension, mental problems, delirium, or epilepsy.

**Figure 8.** Contraindications of manual therapy, TECAR, and HILT therapy.

#### **10. Limitations of the Study**

This study is a description of the theoretical framework of how these techniques work rather than what has been demonstrated by research studies regarding valid research designs and reliable and valid outcome measures. Our research includes studies with various pathologies with which these therapeutic modalities are used, without going into the details of their effectiveness.

#### **11. Conclusions**

Given the many benefits that capacitive and resistive electrical transfer therapy has on muscle disorders, it should be integrated into most recovery protocols to enhance the healing process and to make rehabilitation faster and more straightforward.

However, manual therapy remains as one of the safest and most frequently used methods by physical therapists, with very few contraindications and allowing the therapist to feel and treat with his or her own hands. If combined, these therapies can have much better results, such as the effects of manual therapy (reducing muscle tension, inducing relaxation, and increasing mobility through passive movements performed by the physical therapist) along with the many effects resulting from TECAR muscle tissue therapy (increasing cellular metabolic processes, activating the body's natural repair processes, improving blood flow and improving pain), and also with the effects produced by HILT (accelerating cellular metabolism, faster resorption of pro-inflammatory mediators). HILT is also beneficial in treating muscle diseases, affecting blood circulation and cellular metabolism, thus accelerating tissue regeneration.

TECAR therapy combined with manual therapy in the management of muscle disorders provides excellent coordination in the healing process, which is beneficial for all types of muscle diseases. Through the variety of benefits of each one, more positive results can be obtained, unless used specifically with only one of the two therapies. Moreover, manual therapy combined with HILT appears to have similar effects to the previous combination but is not as pleasant for the patient. TECAR therapy with HILT and manual therapy may be ideal for treating muscle disorders to accelerate healing, maintain tissue elasticity and joint mobility, and restore the patient to pre-injury fitness.

**Author Contributions:** Conceptualisation, D.A.S., N.N., S.T., I.S.S., C.P. and L.P.; methodology, D.A.S., N.N. and S.T.; software, I.S.S. and C.P.; validation, D.A.S., N.N. and S.T., formal analysis, D.A.S., I.S.S., C.P. and L.P.; investigation, D.A.S., N.N. and S.T.; resources, D.A.S. and L.P.; data curation, D.A.S., N.N. and L.P.; writing—original draft preparation, D.A.S., N.N., S.T., I.S.S., C.P. and L.P.; writing—review and editing, D.A.S., N.N. and S.T.; visualisation, D.A.S. and I.S.S.; supervision, D.A.S., N.N., S.T. and I.S.S.; project administration, D.A.S., N.N., S.T., I.S.S., C.P. and L.P.; All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**

### *Article* **Menstrual Cycle Changes Joint Laxity in Females—Differences between Eumenorrhea and Oligomenorrhea**

**Sae Maruyama 1, Chie Sekine 1, Mayuu Shagawa 1, Hirotake Yokota 1, Ryo Hirabayashi 1, Ryoya Togashi 1, Yuki Yamada 1, Rena Hamano 2, Atsushi Ito 2, Daisuke Sato <sup>1</sup> and Mutsuaki Edama 1,\***

**Abstract:** The purpose of this study was to investigate the changes in anterior knee laxity (AKL), stiffness, general joint laxity (GJL), and genu recurvatum (GR) during the menstrual cycle in female non-athletes and female athletes with normal and irregular menstrual cycles. Participants were 19 female non-athletes (eumenorrhea, *n* = 11; oligomenorrhea, *n* = 8) and 15 female athletes (eumenorrhea, *n* = 8; oligomenorrhea, *n* = 7). AKL was measured as the amount of anterior tibial displacement at 67 N–133 N. Stiffness was calculated as change in (Δ)force/Δ anterior displacement. The Beighton method was used to evaluate the GJL. The GR was measured as the maximum angle of passive knee joint extension. AKL, stiffness, GJL, and GR were measured twice in four phases during the menstrual cycle. Stiffness was significantly higher in oligomenorrhea groups than in eumenorrhea groups, although no significant differences between menstrual cycle phases were evident in female non-athletes. GR was significantly higher in the late follicular, ovulation, and luteal phases than in the early follicular phase, although no significant differences between groups were seen in female athletes. Estradiol may affect the stiffness of the periarticular muscles in the knee, suggesting that GR in female athletes may change during the menstrual cycle.

**Keywords:** anterior knee laxity; stiffness; general joint laxity; genu recurvatum

#### **1. Introduction**

Injury to the anterior cruciate ligament (ACL) is a sports injury that occurs more frequently in women than in men [1]. Sex differences in the incidence of ACL injury are attributed in part to the influence of female hormones, the concentrations of which fluctuate during the menstrual cycle [2]. The menstrual cycle is regulated by the female hormones estradiol and progesterone, and is divided into follicular, ovulation, and luteal phases. ACL injury is reportedly more likely to occur during the follicular [3] and ovulation phases [4]. Clarifying the relationship between risk factors for ACL injury and female hormones is therefore an important step in minimizing the risk of such injury.

One potential risk factor for ACL injury in women is joint laxity. Joint laxity has been examined in terms of anterior knee laxity (AKL), general joint laxity (GJL), and genu recurvatum (GR), each of which have been reported to show associations with risk of ACL injury [5–7]. A previous study found that AKL [8,9], GJL [10], and GR [11] were all higher in women than in men. In addition, AKL, GJL, and GR may be altered by changes in the concentrations of female hormones during the menstrual cycle [9,12,13]. Previous studies therefore suggest that changes in joint laxity due to changes in female hormone concentrations may be related to differences in the timing of ACL injury during the menstrual cycle.

**Citation:** Maruyama, S.; Sekine, C.; Shagawa, M.; Yokota, H.; Hirabayashi, R.; Togashi, R.; Yamada, Y.; Hamano, R.; Ito, A.; Sato, D.; et al. Menstrual Cycle Changes Joint Laxity in Females—Differences between Eumenorrhea and Oligomenorrhea. *J. Clin. Med.* **2022**, *11*, 3222. https://doi.org/10.3390/ jcm11113222

Academic Editors: Redha Taiar, Mario Bernardo-Filho and Ana Cristina Rodrigues Lacerda

Received: 6 April 2022 Accepted: 3 June 2022 Published: 5 June 2022

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Some reports have suggested that AKL, which indicates the laxity of the ACL, is altered by changes in hormone levels during the menstrual cycle [9,12,14], while others have reported the AKL shows no significant change [8,15–18]. Likewise, studies have reported both that GJL changes [12,18] and that GJL remains unchanged during the menstrual cycle [17]. Such contradictory findings may be due to the fact that the timings of measurements and subjects differed between studies.

In addition, most previous studies investigating changes in joint laxity during the menstrual cycle have been conducted among women with normal menstrual cycles. Lee et al. examined the effect of oral contraceptive (OC) use on AKL and found that AKL was significantly higher in the non-OC group than in the OC group, and that AKL was increased during the ovulation and luteal phases compared with the early follicular phase [19]. Decreases in levels of female sex hormones due to OC use may thus affect AKL. In addition, it has been reported that 20–30% of Japanese female athletes reported experience menstrual irregularities [20,21] such as oligomenorrhea [22]. To investigate the effects of female hormones on joint laxity in greater detail, women with menstrual irregularities would need to be included in the study. However, to the best of our knowledge, no reports have examined changes in joint laxity during the menstrual cycle among women with menstrual irregularities. Clarification of these issues would contribute to the development of better methods for training and prevention of ACL injuries in accordance with menstrual cycle conditions.

The purpose of this study was to determine changes and differences in joint laxity (AKL, GJL, and GR) during the menstrual cycle among female athletes and non-athletes with normal and irregular menstrual cycles. We hypothesized that AKL, GJL, and GR would all change during the menstrual cycle in female athletes and non-athletes with normal menstrual cycles, and would not change during the menstrual cycle in female athletes and non-athletes with menstrual irregularities.

#### **2. Materials and Methods**

#### *2.1. Participants*

Seventy-one female non-athletes and 27 female athletes affiliated with the university were recruited between July 2020 and July 2021 and administered a questionnaire on inclusion criteria. Inclusion criteria were as follows: (1) no history of injury or surgery involving the osteochondral surfaces, ligaments, tendons, capsule, or menisci of either knee joint; and (2) no use of OCs or other hormonal medications within the 6 months preceding the first day of measurement [23]. Female non-athletes were defined as female who were physically active less than 3 times per week [17]. Non-athletes 19 people (Figure 1) and athlete 15 people (volleyball 10 people, basketball 5 people) (Figure 2) met the inclusion criteria and agreed to participate in the study. This study was approved by the ethics committee at Niigata University of Health and Welfare (approval no. 18467). This study complied with the tenets of the Declaration of Helsinki and was conducted only after obtaining written consent from potential study participants who had been fully informed (in both oral and written form) of the nature of the experiments.

#### *2.2. Classification of the Menstrual Cycle*

Participants were classified into two groups: a eumenorrhea group and an oligomenorrhea group. The eumenorrhea group was defined to include females with menstrual cycles of 25–38 days [22] for the two cycles before and during the experiment, and at least 10 menstrual cycles in the past 12 months [24]. The oligomenorrhea group was defined to include females with menstrual cycles of either less than 24 days or more than 39 days [22] in the menstrual cycle before or during the experiment, or who had nine or fewer menstrual cycles in the past 12 months [24]. The 19 female non-athletes included 11 individuals in the eumenorrhea group (mean age, 21.0 ± 0.7 years; height, 159.3 ± 4.8 cm; weight, 50.1 ± 7.4 kg; cycle length, 31.3 ± 2.1 days) and 8 individuals in the oligomenorrhea group (mean age, 21.3 ± 0.4 years; height, 158.3 ± 4.2 cm; weight, 54.7 ± 9.2 kg; cycle length, 35.4 ± 7.5 days). The 15 female athletes included 8 individuals in the eumenorrhea group

(mean age, 18.8 ± 0.7 years; height, 167.2 ± 6.6 cm; weight, 65.8 ± 10.0 kg; cycle length, 31.0 ± 2.5 days) and 7 individuals in the oligomenorrhea group (mean age, 19.3 ± 0.7 years; height, 167.8 ± 5.7 cm; weight, 60.1 ± 3.6 kg; cycle length, 45.0 ± 12.0 days).

**Figure 1.** Flowchart for selection of female non-athlete participants. AKL, anterior knee laxity; GJL, general joint laxity; GR, genu recurvatum.

**Figure 2.** Flowchart for selection of female athlete participants. AKL, anterior knee laxity; GJL, general joint laxity; GR, genu recurvatum.

#### *2.3. Menstrual Cycle Recording*

Participants were asked to measure their basal body temperature (BBT) with a basal thermometer (Citizen Electronic Thermometer CTEB503L; Citizen Systems Co., Ltd., Tokyo, Japan) every morning for 1–3 months preceding the first day of measurement. To estimate the day of ovulation, participants were given an ovulation test kit (Doctor's Choice One Step Ovulation Test Clear; Beauty and Health Research, Torrance, CA, USA) and asked to use it from the day after the end of menstruation. Participants were asked to record daily BBT, ovulation test kit results, and start and end dates of menstruation in the ONE TAP SPORTS, an athlete's condition management system (Euphoria Co., Ltd., Tokyo, Japan).

#### *2.4. Timing of Measurements*

AKL, stiffness, GJL, and GR were measured a total of eight times each on two consecutive days during each of the four phases of the menstrual cycle (early follicular, late follicular, ovulation, and luteal phases), and the average of values from those two days was used as the measurement value for each phase. Salivary hormone levels were measured only on the first day of each phase. Measurements were taken on two days between 2–4 days after the onset of menstruation in the early follicular phase, on two days between 2–4 days after the end of menstruation in the late follicular phase, on two days between 2–4 days after a positive result from the ovulation test kit day in the ovulation phase, and on two days more than 2 days after the transition to the high-temperature phase of BBT or 1 week after the first measurement in the ovulation phase in the luteal phase. In the luteal phase, if BBT during the 3 days after the estimated ovulation day was at least 0.2 ◦C higher than the average BBT during the first 6 days of menstruation, the BBT was considered biphasic, indicating a transition from the low- to the high-temperatures phase [25]. All measurements were performed between 07:00 and 12:00 to account for diurnal variations.

#### *2.5. Measurement Methods*

#### 2.5.1. Hormone Level Measurement

To measure salivary concentrations of estradiol and progesterone, saliva was collected and analyzed using a saliva collection kit (SalivaBio A; Salimetrics, Carlsbad, CA, USA). Participants were asked to rinse the mouth prior to the start of the experiments, so that no food particles remained in the oral cavity. Saliva was collected at least 10 min after rinsing to prevent dilution of hormone concentrations in saliva. We also asked participants to strictly observe the following prohibitions and precautions during saliva collection: (1) no eating for at least 60 min prior to saliva collection; (2) no alcohol intake for at least 12 h prior to saliva collection; (3) no intake of sugary, acidic or caffeinated beverages prior to saliva collection; (4) no intake of dairy products for at least 20 min prior to saliva collection; (5) no tooth brushing for at least 45 min prior to saliva collection; and (6) no dental treatment within 48 h before saliva collection [26]. Saliva was collected in the mouth for 1 min, then transferred to a saliva collection container (Cryyovial; Salimetrics) using a special straw (Siva Collection Aid; Salimetrics). The saliva sample was immediately stored in a freezer at less than −80 ◦C. Analysis of female hormone concentrations was entrusted to Funakoshi Corporation (Tokyo, Japan). Samples were thawed at room temperature, mixed by vortexing, centrifuged at 1500× *g* for 15 min, and analyzed by enzyme-linked immunosorbent assay using high-sensitivity salivary immunoassay kits (17β-Estradiol Enzyme Immunoassay Kit and Salivary Progesterone Enzyme Immunoassay Kit; Salimetrics). The dilution factor was uniformly 1-fold (undiluted).

#### 2.5.2. Laxity Measurement

AKL was measured as the amount of anterior displacement of the tibia relative to the femur when loads of 67 N, 89 N, 111 N, and 133 N applied to the tibia. AKL was measured using a cruciate ligament function tester (KS Measure KSM-100; Japan Sigmax, Tokyo, Japan), and was performed only on the pivot (non-dominant) foot. Participants were placed in a supine position with the knee joint set in approximately 30◦ of flexion using a goniometer (Goniometer; Nishikawashinwa, Tokyo, Japan). The knee support was placed on the posterior part of the distal thigh and the foot support was placed under the foot. The position of the cruciate ligament function tester was adjusted so that

the patellar contact point was at the center of the knee and the ankle fixation point was at the center of the ankle. The ankle was fixed with a lower limb fixation belt and the lower leg was fixed with a traction belt. After the participants was instructed to relax, measurement was performed by operating the load handle. Five measurements were taken and after discarding the maximum and minimum values, the average of the three remaining measurements was recorded. Measurement of knee joint angle and operation of the load handle were performed by a single researcher (S.M.). The intra-rater reliability of AKL measurement was confirmed to be higher than in our previous study [17]. Stiffness was calculated as change in (Δ)force/Δanterior displacement at 67–89 N, 89–111 N, and 111–133 N loads [17].

GJL was measured using the Beighton method [27]. Mobility was measured at five locations: fifth (little) finger, wrist, elbow, knee, and spine. Assessment criteria were as follows: (1) extension of the fifth finger greater than 90◦; (2) ability to touch the thumb to the forearm, (3) hyperextension of the elbow greater than 10◦; (4) hyperextension of the knee greater than 10◦; and (5) ability to perform forward flexion of the trunk with palm touching the floor in full extension of the knee joint. Criteria (1) to (4) were evaluated as 1 point for each side, and Criterion 5 was evaluated as 1 point, for a total of 9 points. GJL was measured using the goniometer for items based on joint angle. GJL measurements were performed by one researcher (S.M.).

GR was measured using a hyperextension apparatus (Takei Scientific Instrument Co., Niigata, Japan) to evaluate the range of motion of knee extension (Figure 3). Participants were seated in a long sitting position with the hip joint set in about 70◦ of flexion with both upper limbs behind them (Figure 3A). Knee joint extension was defined as 0◦ when the scales for seat height and foot height were the same. The distance from the knee to the heel was adjusted by placing the heel on the footrest (Figure 3B), and the right and left positions of the lower limbs were adjusted to achieve 0◦ of hip adduction (Figure 3C). The proximal patella was fixed with a knee-fixation belt, and foot width was also fixed. Participants were instructed in advance to signal just before the appearance of pain or discomfort in the knee joint, and the knee joint was extended by turning the foot elevation screw at a rate of approximately 1◦·s−<sup>1</sup> or less until the signal was given. At the time the participant gave the signal, the foot was held for 10 s and the value on the scale for foot height was recorded. Maximum angle of passive knee joint extension was later calculated using the change in foot height (H) and the length from the center of the knee to the heel (L) according to the following equation:

### GR [◦] = Arctan (H/L) × 57.2958

After one practice test, five measurements were taken. After discarding the maximum and minimum values, the average of the three remaining measurements was recorded. A rest period of 10 s was provided between each of the five trials. Measurements were taken only for the pivot (non-dominant) foot. GR measurements were performed by one researcher (S.M.).

#### *2.6. Reliability of GR Measurements*

The reliability of GR measurements was examined in 10 knees of 5 adult males (mean age, 23.4 ± 0.8 years; height, 168.1 ± 5.7 cm; weight, 60.9 ± 4.0 kg) and 10 knees of 5 adult females (mean age, 21 ± 0.9 years; height, 166.7 ± 8.6 cm; weight, 59.3 ± 11.9 kg) in this study, none of whom had orthopedic diseases or pain in the lower limbs. GR was measured using the methods described above, with an interval of at least 10 min between measurements by different researchers (S.M. and C.S.) to determine inter-rater reliability and an interval of at least 30 min between measurements by the same researcher (S.M.) for intra-rater reliability, on the same day. Intra- and inter-rater reliabilities were calculated using intraclass correlation coefficient (ICC) (1, 3) and (2, 3), respectively.

**Figure 3.** Position for measurement of genu recurvatum. 1: Knee-fixation belt; 2: foot width fixing part; 3: right/left adjustment of lower limbs; 4: foot elevation screw; L, length from center of knee to heel. The participant was seated on the hyperextension apparatus (Takei Scientific Instrument Co., Niigata, Japan) in a long sitting position with the hip joint set in about 70◦ of flexion with both upper limbs behind them (**A**). Distance from the knee to the heel was adjusted by placing the heel on the footrest (**B**), and positions of the lower limbs were adjusted to the left/right to achieve 0◦ of hip adduction (**C**). The proximal patella was fixed with the knee-fixation belt, and foot width was also fixed. Participants were instructed in advance to signal just before the appearance of pain or discomfort in the knee joint, and the knee joint was extended by turning the foot elevation screw at a rate of approximately 1◦·s−<sup>1</sup> or less until that signal was given. At the time the signal was given, foot height was recorded. Maximum angle of passive knee joint extension was calculated later based on the result recorded.

#### *2.7. Statistical Analysis*

Statistical analyses were performed using SPSS version 27.0 (IBM Corp, Tokyo, Japan). Split-plot repeated-measures analysis of variance (ANOVA) was conducted to com-pare salivary estradiol and progesterone concentrations, AKL, stiffness, GJL, and GR menstrual cycle phases in female non-athletes and female athletes, and to compare eumenor-rhea and oligomenorrhea groups (subject factors [eumenorrhea group, oligomenorrhea group] vs. cycle phase factors [early follicular phase, late follicular phase, ovulation phase, luteal phase]). When an interaction or main effect of the subject factor or the cycle phase factor was identified, one-way repeated-measures ANOVA was used for comparison within cycle phase factors, and statistical processing was performed by the Bonferroni method as a posttest. In addition, statistical processing was performed by the independent samples *t*-test and Mann-Whitney U test as a post-test for comparison within subject factors. Probability values of 5% were considered statistically significance.

#### **3. Results**

#### *3.1. Female Non-Athletes*

In salivary estradiol, split-plot repeated-measures ANOVA showed no interactions and no main effects of subject factor, but a main effect of the cycle phase factor [F (2.197, 37.343) = 7.23, *p* = 0.002, ηp2 = 0.30]. The results of Bonferroni post hoc testing showed that salivary estradiol concentrations were significantly higher in the ovulation and luteal phases than in the early follicular phase (*p* = 0.006 and *p* = 0.002, respectively) (Table 1).

In salivary progesterone, split-plot repeated-measures ANOVA showed an interaction [F (1.345, 22.872) = 3.97, *p* = 0.048, ηp2 = 0.19]. One-way repeated-measures ANOVA and Bonferroni post hoc testing showed that salivary progesterone concentrations was significantly higher in the luteal phase than in the early follicular phase and ovulation phases in the eumenorrhea group (*p* = 0.026 and *p* = 0.040, respectively). Results from the independent sample *t*-test and post hoc Mann-Whitney U-test showed that salivary progesterone concentrations were significantly higher in the eumenorrhea group than in the oligomenorrhea group during the luteal phase (*p* = 0.035) (Table 1).

Values are presented as means ± SD. *<sup>a</sup>*—Statistically significant difference compared with early follicular phase in female non-athletes (*p* = 0.006). *<sup>b</sup>*—Statistically significant difference compared with early follicular phase in female non-athletes (*p* = 0.002). *<sup>c</sup>*—Statistically significant difference compared with early follicular phase in the eumenorrhea group of female non-athletes (*p* = 0.026). *<sup>d</sup>*—Statistically significant difference compared with ovulation phase in the eumenorrhea group of female non-athletes (*p* = 0.040). *<sup>e</sup>* —Statistically significant difference compared with oligomenorrhea in the luteal phase of female non-athletes (*p* = 0.035). *<sup>f</sup>* —Statistically significant difference compared with the early follicular phase in female athletes (*p* = 0.039). *<sup>g</sup>*—Statistically significant difference compared with the early follicular phase in female athletes (*p* = 0.005). *<sup>h</sup>*—Statistically significant difference compared with the late follicular phase in female athletes (*p* = 0.001). *<sup>i</sup>* —Statistically significant difference compared with the ovulation phase in female athletes (*p* = 0.022).

In AKL, the results of split-plot repeated-measures ANOVA showed no interactions or main effects of subject or cycle-phase factors at any loadings (Table 2).

Values are presented as means ± SD.

In stiffness, split-plot repeated-measures ANOVA showed no interactions and no main effects of cycle-phase factors between any loadings, but a main effect of the subject factor was seen only between 89–111 N [F (1, 17) = 6.61, *p* = 0.020, ηp2 = 0.28] and 111–133 N [F (1, 17) = 9.48, *p* = 0.007, ηp2 = 0.36] loadings. The results of the Bonferroni post hoc testing showed that stiffness at 89–111 N and 111–133 N was significantly higher in the oligomenorrhea group than in the eumenorrhea group (*p* = 0.020 and *p* = 0.007, respectively) (Table 3).

Values are presented as means ± SD. *<sup>a</sup>*—Statistically significant difference compared with the eumenorrhea group (*p* = 0.020). *<sup>b</sup>*—Statistically significant difference compared with the eumenorrhea group (*p* = 0.007).

The results of split-plot repeated-measures ANOVA about GJL and GR showed no interactions or main effects of subject or cycle-phase factors (Tables 4 and 5).

Values are presented as means ± SD.

Values are presented as means ± SD. *<sup>a</sup>*—Statistically significant difference compared with the early follicular phase in female athletes (*p* = 0.050). *<sup>b</sup>*—Statistically significant difference compared with the early follicular phase in female athletes (*p* = 0.011). *<sup>c</sup>*—Statistically significant difference compared with the early follicular phase in female athletes (*p* = 0.004).

#### *3.2. Female Athletes*

In salivary estradiol, split-plot repeated-measures ANOVA showed no interactions and no main effects of subject factor, but a main effect of the cycle-phase factor [F(3, 39) = 5.33, *p* = 0.004, ηp2 = 0.29]. The results of Bonferroni post hoc testing showed that salivary estradiol concentrations were significantly higher in the luteal phase than in the early follicular phase (*p* = 0.039) (Table 1).

In salivary progesterone, split-plot repeated-measures ANOVA showed no interactions and no main effects of subject factor, but a main effect of the cycle-phase factor [F(1.500, 19.502) = 14.38, *p* = 0.0004, ηp2 = 0.53]. The results of Bonferroni post hoc testing showed that salivary progesterone concentrations were significantly higher in the luteal phase than in the early follicular, late follicular, and ovulation phases (*p* = 0.005, *p* = 0.001 and *p* = 0.022, respectively) (Table 1).

The results of split-plot repeated-measures ANOVA about AKL, stiffness, and GJL showed no interactions or main effects of subject or cycle-phase factors at any loadings (Tables 2–4).

In GR, split-plot repeated-measures ANOVA showed no interactions and no main effects of the subject factor, but a main effect of the cycle-phase factor [F (1.929, 25.074) = 13.32, *p* = 0.0001, ηp2 = 0.51]. The results of Bonferroni post hoc testing showed that GR was significantly higher in the late follicular, ovulation, and luteal phases than in the early follicular phase (*p* = 0.050, *p* = 0.011 and *p* = 0.004, respectively) (Table 5).

#### *3.3. Reliability of GR Measurement*

ICC (1, 3) was 0.828 and ICC (2, 3) was 0.854. According to the criteria of Landis et al. [28], reliability is considered "almost perfect" for ICCs of 0.81 or more, so the reliabilities of GR measurements in this study were considered almost perfect.

#### **4. Discussion**

To the best of our knowledge, this represents the first study to examine changes in joint laxity during the menstrual cycle among females with menstrual irregularities. The main findings of this study were that stiffness was significantly higher in the oligomenorrhea group than in the eumenorrhea group, although no significant difference in stiffness was seen between cycle phases when limited to female non-athletes. GR was significantly higher in the late follicular, ovulation, and luteal phases than in the early follicular phase, although no difference between groups was seen when limited to female athletes. No significant differences in AKL or GJL were between groups or cycle phases in either female non-athletes or female athletes.

Stiffness did not change with the menstrual cycle in female non-athletes; however, it was significantly higher in the oligomenorrhea group than the eumenorrhea. Karageanes et al. considered that repetition of the menstrual cycle (hormonal stimulation) may exert long-term effects on connective tissues, resulting in changes to estradiol receptor sensitivity or an unraveling effect in which ligaments gradually become looser [16]. In this study, the duration of exposure to estradiol may have been shorter in the oligomenorrhea group with longer menstrual cycles than in the eumenorrhea group. If the duration of exposure to estradiol affected the tensile properties of the ACL, stiffness may have been higher in the oligomenorrhea group than in the eumenorrhea group. Stiffness can be calculated and quantified from the load-displacement curve obtained from AKL measurements and has been suggested to be related to clinical end-feel [29]. Three phases are observed in the load-displacement curve: early phase: middle phase: and late phase, the late phase is considered to represent the terminal stiffness of the joint in which the ACL is fully involved in restraining tibial anterior displacement [29]. Davey et al. reported that a 1-standard deviation (SD) decrease in ACL stiffness was associated with a 2.37-fold increased risk of contralateral injury after initial ACL injury [30]. In addition, the incidence of ACL injury is reportedly higher among women with normal menstruation than among those using OCs [31]. Such considerations suggest that female non-athletes with oligomenorrhea may have fewer risk factors for ACL injury than female non-athletes with eumenorrhea.

GR in female athletes was significantly higher in the late follicular, ovulation, and luteal phases than in the early follicular phase, although no difference was evident between eumenorrhea and oligomenorrhea groups. These results support previous findings that GR changes during the menstrual cycle [12,18]. Estradiol receptors are present in the human ACL [32], myofibers of skeletal muscle and capillary endothelial cells [33]. Previous studies investigating changes in muscle stiffness during the menstrual cycle have reported that hamstring extensibility (straight leg raising angle) was higher during the ovulation phase compared to the early follicular phase [34], and muscle stiffness of the vastus medialis and semitendinosus muscles was higher during the ovulation phase compared to the luteal phase [35]. Avrillon et al. reported that the shear modulus of the semimembranosus muscle was lower among figure skaters, taekwondo practitioners, soccer players, and fencers than among non-athletes [36]. This suggests that female athletes with lower muscle stiffness may be more susceptible to changes in joint laxity than non-athletes. Therefore, it is possible that estradiol may have altered muscle stiffness, resulting in altered GR in female athletes during the menstrual cycle. The results of this study thus suggest that female athletes may be at increased risk of ACL injury from the late follicular phase to the luteal phase. In the future, a better understanding of the menstrual cycle of female athletes will be needed to develop training methods adapted to the cyclical changes in body structure and methods for preventing ACL injury.

The AKL did not change during the menstrual cycle in either female non-athletes or female athletes, and no difference was seen between eumenorrhea and oligomenorrhea groups. The results of this study support previous studies that AKL does not change during the menstrual cycle [8,15–17]. Lee et al. found that AKL was significantly higher in the non-OC group than in the OC group and that AKL changed only in the non-OC group [19]. In the present study, no difference in estradiol concentration was identified between eumenorrhea and oligomenorrhea groups, suggesting that no group differences may exist in AKL. GJL did not change during the menstrual cycle in either female nonathletes or female athletes, and no difference was apparent between eumenorrhea and oligomenorrhea groups. The results of this study differed from those of previous studies, which showed that GJL changed during the menstrual cycle [12,18]. GJL can be congenital, occurring as a part of connective tissue diseases such as Marfan's syndrome, Ehlers-Danlos syndrome, and benign joint hypermobility syndrome [37], or acquired, resulting from stretching of the capsular ligament due to repetitive microtrauma or repetitive use during sports activities [38]. GJL is thus suggested to be highly susceptible to congenital laxity or sports history, but less susceptible to female hormones during the menstrual cycle.

Several limitations to the present study must be considered when interpreting the results. First, considering the characteristics of the experimental apparatus and the safety of participants, GR was evaluated based on the subjective sensations of participants. In this study, GR was measured by extending the knee joint until just before the appearance of pain or discomfort in the knee joint, so pain or intrinsic receptive sensation may have been affected. The pain threshold reported does not change during the menstrual cycle [39], but intrinsic receptive sensation in the knee joint is reported to decrease in the early follicular phase compared to the luteal phase [40]. However, the reliability of GR measurement appeared to be high in this study, so the method of measuring GR in this study was considered to be highly valid. A second limitation was that we could not control the amount of activity of female athletes. In this study, female athletes were tested throughout a single season, because the study period was extended due to the coronavirus disease 2019 pandemic. The activity levels of female athlete participants may thus have differed between training and competition periods, which may have contributed to discrepancies in the results for AKL, GJL, and GR. Therefore, when assessing joint laxity in female athletes, consideration must be given to not only the effects of the menstrual cycle, but also the amount of activity during the season. A third limitation was the sample size. In the present study, joint laxity was measured eight times in four phases: early follicular phase, late follicular phase, ovulation phase, and luteal phase. Of the 71 female nonathletes and 27 female athletes recruited, only 19 female non-athletes and 15 female athletes completed the experiment. Some degree of caution is thus warranted when interpreting the present results. However, by measuring joint laxity at multiple time points throughout the menstrual cycle, we were able to more accurately investigate changes in joint laxity during the menstrual cycle. A fourth limitation was that the participants were limited to university students and university athletes. Previous studies have reported that age may affect the value of joint laxity [10,41]. Therefore, the results of this study may not be applicable to non-university age groups. Future studies should be conducted not only in university age group but also in middle and high school age groups.

#### **5. Conclusions**

In this study, stiffness was significantly higher in the oligomenorrhea group than in the eumenorrhea group when limited to female non-athletes. GR was significantly higher in the late follicular phase, ovulation phase, and luteal phase compared to the early follicular phase when limited to female athletes. Future studies need to clarify the effects of the menstrual cycle in female athletes and develop training methods for injury prevention that are adapted to cyclical changes in female body structure.

**Author Contributions:** Conceptualization, S.M. and M.E.; methodology, S.M. and M.E.; validation, S.M., C.S., M.S., H.Y., R.H. (Ryo Hirabayashi), R.T., Y.Y. and M.E.; formal analysis, S.M. and M.E. investigation, S.M., C.S., M.S. and M.E.; data curation, S.M.; writing—original draft preparation, S.M.; writing—review and editing, M.E., C.S., M.S., H.Y., R.H. (Ryo Hirabayashi), R.T., Y.Y., R.H. (Rena Hamano), A.I. and D.S.; visualization, S.M.; project administration, M.E.; funding acquisition, M.E. All authors have read and agreed to the published version of the manuscript.

**Funding:** This study was supported by a Grant-in-Aid for Scientific Research (19K11358) from the Japan Society for the Promotion of Science (JSPS) and commissioned by the Japan Sports Agency (Female Athletes Development and Support Projects 2020).

**Institutional Review Board Statement:** The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Niigata University of Health and Welfare (18467—26 August 2020).

**Informed Consent Statement:** Informed consent was obtained from all subjects.

**Data Availability Statement:** The data that support the findings of this study are available from the corresponding author.

**Acknowledgments:** The authors want to acknowledge and thank all female volunteers and all female college athletes who participated in this study.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**

### *Article* **Evidence-Based Surgical Treatment Algorithm for Unstable Syndesmotic Injuries**

**Markus Regauer 1,2,\*, Gordon Mackay 3, Owen Nelson 4, Wolfgang Böcker <sup>1</sup> and Christian Ehrnthaller <sup>1</sup>**

	-<EMAIL_ADDRESS>
**Abstract:** Background: Surgical treatment of unstable syndesmotic injuries is not trivial, and there are no generally accepted treatment guidelines. The most common controversies regarding surgical treatment are related to screw fixation versus dynamic fixation, the use of reduction clamps, open versus closed reduction, and the role of the posterior malleolus and of the anterior inferior tibiofibular ligament (AITFL). Our aim was to draw important conclusions from the pertinent literature concerning surgical treatment of unstable syndesmotic injuries, to transform these conclusions into surgical principles supported by the literature, and finally to fuse these principles into an evidence-based surgical treatment algorithm. Methods: PubMed, Embase, Google Scholar, The Cochrane Database of Systematic Reviews, and the reference lists of systematic reviews of relevant studies dealing with the surgical treatment of unstable syndesmotic injuries were searched independently by two reviewers using specific terms and limits. Surgical principles supported by the literature were fused into an evidence-based surgical treatment algorithm. Results: A total of 171 articles were included for further considerations. Among them, 47 articles concerned syndesmotic screw fixation and 41 flexible dynamic fixations of the syndesmosis. Twenty-five studies compared screw fixation with dynamic fixations, and seven out of these comparisons were randomized controlled trials. Nineteen articles addressed the posterior malleolus, 14 the role of the AITFL, and eight the use of reduction clamps. Anatomic reduction is crucial to prevent posttraumatic osteoarthritis. Therefore, flexible dynamic stabilization techniques should be preferred whenever possible. An unstable AITFL should be repaired and augmented, as it represents an important stabilizer of external rotation of the distal fibula. Conclusions: The current literature provides sufficient arguments for the development of an evidence-based surgical treatment algorithm for unstable syndesmotic injuries.

**Keywords:** syndesmosis; anterior inferior tibiofibular ligament; high ankle sprain; rotational instability; posterior malleolus; stabilization; anatomic repair; syndesmotic screw; suture-button; internal bracing; treatment algorithm

#### **1. Introduction**

An increasing interest in the treatment of unstable syndesmotic injuries during the last decade has led to an enormous amount of literature not easy to review [1–171]. Syndesmosis as a search term in PubMed, for example, currently revealed 1271 results as of 28 October 2021.

The ligaments stabilizing the inferior tibiofibular syndesmosis prevent excess fibular motion in multiple directions: anterior-posterior translation, lateral translation, craniocaudal translation, and internal and external rotation [6,62,63,68,79,164]. Appropriate fibular position and limited rotation are necessary for normal syndesmotic function and

**Citation:** Regauer, M.; Mackay, G.; Nelson, O.; Böcker, W.; Ehrnthaller, C. Evidence-Based Surgical Treatment Algorithm for Unstable Syndesmotic Injuries. *J. Clin. Med.* **2022**, *11*, 331. https://doi.org/10.3390/ jcm11020331

Academic Editors: Antonio Frizziero and Redha Taiar

Received: 14 November 2021 Accepted: 5 January 2022 Published: 10 January 2022

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talar position within the ankle mortise [66]. Reconstruction of unstable syndesmotic injuries is not trivial, and there are no generally accepted treatment guidelines [18,63,80,119]. Thus, there still remain considerable controversies regarding diagnosis, classification, and treatment of unstable syndesmotic injuries [63,119,149]. The most common controversies regarding surgical treatment are related to screw fixation versus dynamic fixation, the use of reduction clamps, open versus closed reduction, and the role of the posterior malleolus and of the anterior inferior tibiofibular ligament (AITFL).

Although several studies have clearly shown serious problems concerning the use of syndesmotic screws, this method is still considered the gold standard for treatment of unstable syndesmotic injuries by the majority of orthopedic and trauma surgeons [10,12,18,19,24,27,30,39,51,53,64,70,148,159]. This controversy may be explained by an obvious lack of further education and training, by the misconception that this surgical technique is simple and easy to perform, and by the fact that syndesmotic screws still represent the cheapest solution, at least considering the short term [115].

Alternative methods for treatment of unstable syndesmotic injuries reported in literature include syndesmotic hooks or hook plates [45,160,166], transfixation bolts [162], various suture button constructs [5,8,38,94,95,106,117,120,131,132,141,142,165], ligament bracing [58,80,98,119,135,140], tendon autograft [25,56,91,98] or even allograft reconstruction [35]. During the last decades, several studies have clearly shown superior results after flexible dynamic syndesmotic stabilization compared to the use of syndesmotic screws with regard to accuracy of reduction, functional outcome, and even development of posttraumatic ankle arthritis [9,32,34,48,57,72,76,94,111,124,134,171].

Therefore, our aim was to draw important conclusions from the pertinent literature concerning surgical treatment of unstable syndesmotic injuries, to transform these conclusions into surgical principles supported by literature, and finally to fuse these principles into an evidence-based surgical treatment algorithm.

#### **2. Materials and Methods**

From 1 October 2019 to 28 October 2021, the first and senior authors (M.R. and C.E.) independently searched PubMed, Embase, Google Scholar, The Cochrane Database of Systematic Reviews, and the reference lists of systematic reviews of relevant studies dealing with the surgical treatment of unstable syndesmotic injuries. The mentioned databases were selected because they represent the prevalent and generally accepted databases used for medical research. The following search terms listed in alphabetical order were used: anatomic reduction, anatomic repair, ankle fracture, anterior inferior tibiofibular ligament (AITFL), augmentation, diastasis screw, flexible stabilization, high ankle sprain, InternalBrace, ligament bracing, positioning screw, posterior malleolus, rotational stability, suture button, syndesmo\*, syndesmosis, syndesmotic screw, tibiofibular\*, tightrope, and treatment algorithm. Only articles published in English, German, or Spanish language were included. Other than language, there were no further restrictions for the inclusion of articles. Letters to the editors, short comments, incomplete, or inaccessible full-text articles were excluded. Included articles were assigned to the following main topics:

After assessment of the scientific quality of the assigned articles, we tried to draw important conclusions from the pertinent literature concerning the surgical treatment of unstable syndesmotic injuries. Then, we transformed these conclusions into clinically relevant surgical principles supported by literature, and finally, we fused these principles into a surgical treatment algorithm.

#### **3. Results**

A total of 171 articles were included for further considerations [1–171]. Among them, 47 articles concerned syndesmotic screw fixation and 41 dynamic fixations of the syndesmosis. Twenty-five studies compared screw fixation with dynamic fixations, and seven out of these comparisons were randomized controlled trials [9,32,34,72,76,111,124]. Nineteen articles addressed the posterior malleolus, 14 the role of the AITFL, and eight the use of reduction clamps.

#### *3.1. Importance of Anatomic Reduction*

Malreduction of the distal tibiofibular syndesmosis still remains a common complication associated with the surgical management of ankle fractures [23,31]. Syndesmotic malreduction can lead to severe alterations in the biomechanics of the ankle and thereby to chronic pain and premature degenerative changes of the ankle joint [31]. Therefore, ankle fractures with need for syndesmotic stabilization are still associated with a high rate of secondary osteoarthritis [118]. As early as 1961, Willenegger stated that posttraumatic osteoarthritis of the ankle almost always is due to an incongruity between the ankle mortise and the talus and not due to an intraarticular fracture itself [162]. He reported on 31 of 32 cases that rapidly developed severe posttraumatic ankle arthritis even after only slight malreduction of the ankle mortise [162]. Several well-known studies confirmed Willenegger's early observations, and today, it is generally accepted that even a small syndesmotic displacement of less than 1 mm can have devastating consequences for the rapid development of posttraumatic ankle arthritis [1,59,62,65,100,102,111,116,123,153]. Significant increases in tibiotalar contact pressures occur when external rotation stresses are added to axial loading in an unstable tibiofibular syndesmosis. Moderate and severe syndesmotic injuries are associated with a significant increase in mean contact pressure combined with a shift in the center of pressure and rotation of the fibula and talus. In this context, simple syndesmotic injuries represent partial ruptures without signs of instability in the clinical and radiological evaluation compared to moderate and severe syndesmotic injuries. Moderate syndesmotic injuries show clinical signs of dynamic instability without static dislocation in the radiographic evaluation, and severe injuries show signs of dislocation of the fibula in the incisura tibiofibularis even in the static examinations.

Considerable changes in ankle joint kinematics and contact mechanics may explain why unstable syndesmotic injuries take longer to heal and are more likely to develop long-term dysfunction and ankle arthritis [65]. Moreover, in the long run, post-traumatic ankle osteoarthritis in known to have a large and negative impact on the patients´ quality of life [172]. The single most important prognostic factor after unstable injury of the distal tibiofibular syndesmosis with or without fracture is anatomic reduction of the distal fibula and fitting into the tibial incisura [112]. Therefore, anatomic reduction of an injured syndesmosis is crucial for an optimal long-term clinical result [7,13,31,151]. In this context, anatomic reduction is defined as complete restoration of the physiological anatomy in the first place but does also imply recovery of the physiologic tension of the repaired ligamentous structures.

Main conclusion: Anatomic reduction is crucial for the long-term results regarding functional outcome and development of posttraumatic ankle osteoarthritis.

#### *3.2. Closed vs. Open Reduction under Direct Visualization*

To reliably achieve anatomic reduction of the syndesmosis, open reduction of the AITFL under direct visualization has been advocated, as there is still a lack of appropriate examination techniques to confirm anatomic closed reduction during surgery [26,87,98,103,119,127,143,150]. Tornetta showed that the anterolateral articular surface of the distal tibia to the anteromedial fibular articular surface is an accurate visual landmark for anatomic reduction of the syndesmosis [143]. Another advantage of open reduction under direct visualization is the opportunity to avoid posttraumatic anterolateral impingement syndrome by removing torn parts of the AITFL out of the joint. And aside

from that, we should remember that the main goal in the treatment of unstable syndesmotic injuries is to avoid osteoarthritis and not scars.

Main conclusion: Open reduction by direct visualization is strongly recommended.

#### *3.3. Role of Reduction Clamps*

Several studies and reports have clearly shown that it is possible and even highly likely to over-compress the syndesmosis when using reduction clamps or forceps [26,36,60,82,85,107,121,156]. In this context, over-compression is defined as any sign of displacement of the talus out of the mortise due to compression of the fibula against the tibia even in correct position of the fibula within the incisura. Haynes et al. demonstrated a significant correlation between increased clamp forces and syndesmotic over-compression and determined objective forces that lead to over-compression of the syndesmosis [60]. Another study by Miller demonstrated that intraoperative clamping and fixation can cause statistically significant malreduction of the syndesmosis [85]. This should alert clinicians that clamp and screw placement can cause iatrogenic malreduction of the syndesmosis. These dangers occur with specific clamp and screw angles in particular. Mahapatra reported that over-compression of the syndesmosis can even cause significant subluxation of the talus [82]. Therefore, care should be taken to avoid over-compression by use of reduction clamps, as this may affect ankle motion and functional outcomes. Cadaver experiments by Phisitkul et al. showed that clamp placement in the neutral anatomical axis reduced the syndesmosis most accurately, but nevertheless, over-compression was frequently observed. Placing the clamp obliquely malreduced the unstable syndesmosis [107]. Furthermore, based on the results of his recent cadaveric study, Rushing stated that inherent variabilities in the applied clamp force by surgeons appear to contribute to the unacceptably high coronal syndesmotic malreduction rate [121]. Goetz et al. have shown that Achilles tension mitigates fibular malalignment measured in cadaveric studies of syndesmotic clamping [53].

In our experience, it seems to depend on the stability of the posterior malleolus and the medial and lateral collateral ankle ligaments if significant over-compression with consecutive dislocation of the talus is possible or not, but this theory has not been proven so far. Cherney described that a stable posterior malleolus does not have a protective effect against over-compression [26]. In our opinion, this might be due to unrecognized additional injuries to the collateral ankle ligaments. Additionally, from an anatomic point of view, there is no physiologic dynamic force leading to displacement of the syndesmosis and therefore needing neutralization by a reduction clamp. As early as 1953, Costigan stated that reduction of diastasis of the ankle mortise is a very simple procedure, not requiring a reducer or any other form of mechanical device [37]. Therefore, at least in acute cases, the surgeon should prefer to analyze the real reasons preventing easy reduction of the syndesmosis instead of increasing the force of reduction clamps.

Main conclusions: There is a high risk for over-compression and malreduction of the syndesmosis by use of reduction clamps or forceps. Therefore, at least in acute cases, the use of reduction clamps or forceps should be avoided whenever possible.

#### *3.4. Role of Syndesmotic Screws*

Syndesmotic screws, also referred to as diastasis screws, situational screws, transfixation screws, trans-syndesmotic screws, or positioning screws, have been used at least since 1947 [37]. Therefore, surgical treatment with syndesmotic screw fixation has been performed for several decades now, and this method is still considered the gold standard of treatment of unstable syndesmotic injuries by the majority of orthopedic and trauma surgeons [5,61,67,125,151,159,162,163,169,170]. However, there is still an ongoing discussion concerning ideal reference points and anatomic landmarks for optimal positioning of syndesmotic screws [74,75]. The risk of malpositioning of syndesmotic screws is very high, and a lack of standard radiological or physical references for accurate syndesmotic screw placement is a potential contributing factor in syndesmotic screw malpositioning [75]. Furthermore, several studies have clearly shown serious problems concerning the use of syndesmotic screws due to malreduction of the ankle mortise or high complication rates after syndesmotic screw removal, for example, [10,12,24,39,51,54,70,100,123,148]. Ovaska analyzed patients with malreduced ankle fractures undergoing re-operation and showed that the most common indication for re-operation was syndesmotic malreduction in 59% of cases [100]. In another series of 160 consecutive patients who underwent syndesmosis screw fixation, 13 patients needed revision surgery. Among them, the incidence of recurrent diastasis of the ankle mortise was 92% [12]. Gardner evaluated twenty-five patients with ankle fractures and syndesmotic instability who had open reduction and syndesmotic fixation [51]. A total of 52% of syndesmoses were malreduced on CT scan but went undetected by plain radiographs. Radiographic measurements did not accurately reflect the status of the distal tibiofibular joint in this series of ankle fractures. Furthermore, post-reduction radiographic measurements were inaccurate for assessing the quality of the reduction [51]. In a prospective randomized controlled multicenter trial with 103 patients, the rate of malreduction using screw fixation was 39% [124]. Therefore, especially due to the repeatedly reported high risk of malreduction, the first-line use of syndesmotic screws as a gold standard for the treatment of unstable syndesmotic injuries should be reconsidered.

Main conclusions: The first-line use of syndesmotic screws as a gold standard for the treatment of unstable syndesmotic injuries should be reconsidered. Syndesmotic screws should be used only as a salvage procedure.

#### *3.5. Role of Flexible Dynamic Stabilization Techniques*

The currently emerging surgical techniques for flexible dynamic stabilization of the syndesmosis are not new regarding their principles, but the available implants provided by industry enabling low-risk and straightforward surgery have significantly improved over the past two decades [5,8,9,33,95,139].

As early as 1961, Willenegger already stated that the preservation of the natural elasticity of the syndesmosis is of greatest importance not only for the final results but also for the initial postsurgical treatment. Accordingly, he refused the use of the rigid transfixation bolt [162]. However, at that time, there was a lack of suitable alternative implants. In 1955, Schumann developed a kind of early precursor of suture-button constructs consisting of two steel plates placed over the medial and lateral malleolus connected via a transmalleolar tensioning wire bolt [131]. This indicates that even at that early time, surgeons were searching for flexible alternatives to the rigid screw or bolt fixations. Some decades later, in 1991, Seitz et al. reported on the repair of the tibiofibular syndesmosis with a flexible implant consisting of a double thickness of No. 5 braided polyester suture tied over polyethylene buttons situated medially and laterally [132].

The currently most widely-used flexible dynamic stabilization device is the knotless syndesmosis TightRope® implant system produced by Arthrex (Naples, FL, USA). Recently, this device has attracted a great deal of even public attention due to an extremely accelerated return to play in high-level athletes after surgical stabilization of high ankle sprains [104]. Tightrope surgeries have been brought into the spotlight known as "Tua surgery" by the circumstances of the Alabama Crimson Tide's 2018 football season. Starting quarterback Tua Tagovailoa suffered a high ankle sprain on 1 December 2018, and the following day, his injured right ankle was stabilized by Norman Waldrop using two knotless syndesmosis TightRope® implant systems. Tagovailoa returned to play just 27 days after surgery to lead the Alabama Crimson Tide football team to a win over Oklahoma in the College Football Playoff semifinal on 29 December 2018.

During the last decades, several studies have clearly shown superior results after flexible dynamic syndesmotic stabilization compared to the use of syndesmotic screws with regard to accuracy of reduction, functional outcome, and even development of posttraumatic ankle arthritis [9,29,32,34,48,49,55,57,69,71,72,76,83,94,102,111,115,124,125,129,130,132,138,171]. Seven of these comparisons were randomized controlled trials [9,32,34,72,76,111,124]. In 2019, for example, Sanders showed that the rate of malreduction using screw fixation was

39% compared with 15% using TightRope® fixation, and the reoperation rate was much higher in the screw group compared with TightRope® (30% vs. 4%, *p* = 0.02) with the difference driven by the rate of implant removal [124]. With deliberate malreduction in a cadaver model, Westermann reported that suture-button fixation of the syndesmosis results in less post-fixation displacement compared with screw fixation. The suture button's ability to allow for natural correction of deliberate malreduction was greatest with posterior off-axis clamping [161]. Therefore, dynamic syndesmotic fixation may even mitigate clamp-induced malreduction. A systematic review of suture-button versus syndesmotic screw in the treatment of distal tibiofibular syndesmosis injury by Zhang et al. showed that the suture-button device could lead to better objective range of motion measurements and earlier return to work. Besides, the suture-button fixation group had lower rates of implant removal, implant failure, and malreduction [171].

A randomized trial by Anderson et al. comparing suture-button with single syndesmotic screw for syndesmosis injury attested that patients treated with a suture-button device had higher AOFAS scores, OMA scores, and EQ-5D Index scores as well as better VAS scores for pain during walking and pain during rest. Moreover, the suture-button group had less widening seen radiographically at two years than did the patients in the syndesmotic screw group [9]. Five years after syndesmotic injury treated with either suturebutton or syndesmotic screw within a randomized controlled trial, Ræder et al. found better AOFAS and OMA scores and even lower incidence of ankle osteoarthritis in the suture-button group [111].

These long-term results clearly favor the use of suture-button devices when treating an acute syndesmotic injury. In a recent meta-analysis performed by Shimozono, the suture-button technique resulted in improved functional outcomes as well as lower rates of broken implant and joint malreduction. Based on these findings, the suture-button technique warrants a grade A recommendation by comparison with the syndesmotic screw technique for the treatment of syndesmosis injuries [134].

Main conclusion: Use flexible dynamic stabilization techniques for treatment of unstable syndesmotic injuries whenever possible.

#### *3.6. Role of the AITFL*

According to the aforementioned literature, it is possible to achieve very good results in the treatment of unstable syndesmotic injuries using suture-button devices in most cases. However, a study by Clanton recently showed that in some cases, it might not be possible to sufficiently stabilize sagittal translation of the distal fibula by one TightRope® and especially rotary instability even by use of two such flexible dynamic suture-button devices [29]. These observations were confirmed in a biomechanical study by Goetz et al., who reported that flexible trans-syndesmotic fixation alone was found to be insufficient for restoring rotational stability to the ankle or preventing sagittal plane displacement of the distal fibula, and thus, repairs to simulate anatomic structures disrupted during a syndesmosis injury were required to restore rotational stability [55]. Moreover, Clanton showed that isolated injuries to the AITFL resulted in the most substantial reduction of resistance to external rotation and that even isolated injuries to the AITFL alone may lead to significant external rotary instability of the ankle mortise [29]. Recently, these findings were confirmed by a cadaveric robotic study by Patel, who showed that ankle instability is similar after both isolated AITFL and complete syndesmosis injury and can persist after suture-button fixation in the sagittal plane in response to an inversion stress [105].

We have also experienced these problems clinically, and therefore, we started to augment our repairs of the AITFL by use of an *Internal*BraceTM (Arthrex, Naples, FL, USA) in 2013 [119]. Shoji, Teramoto, and Hajewski published a similar surgical technique for ligament augmentation of the AITFL in 2018 and 2019, respectively [58,135,140].

Even earlier, Nelson reported in 2006 on the importance of the AITFL and described two methods for an anatomic repair or reconstruction of the AITFL [98]. However, at that time, there were no suitable implants available, so that this technique was not widely adopted. This article by Nelson was a report of 50 unselected consecutive unstable ankle fractures in which he specifically visually examined the injured AITFL and described a technique of direct visual reduction and flexible repair of the syndesmotic disruption using autograft or sutures secured to bone with traditional screws. Syndesmotic screw fixation of transmalleolar ankle fractures was not necessary in any of the 50 cases when the AITFL was repaired directly by the techniques described. In this unselected consecutive series of patients, Nelson documented a 100% incidence of injury of the AITFL independent of the fracture classification (Weber A, B, and C fractures were included in the study) [98]. The total incidence of bony avulsions of the AITFL was 26%, consisting of an 18% incidence of fibular avulsions (Wagstaffe fragments) and an 8% incidence of tibial avulsions (Tubercule de Chaput fragments). Based upon that clinical experience and continuing interest in the syndesmotic ligaments, it was Nelson's conviction that the AITFL is ruptured in virtually 100% of unstable ankle fractures and that direct visual reduction and repair of ligament disruptions and bone avulsions results in reliable restoration of ankle anatomy and stability. Consequently, Littlechild advocated that consideration should also be given to reconstruction of the AITFL to augment the syndesmosis fixation, which may provide a stronger restoration of ankle stability compared to repairing the posterior inferior tibiofibular ligament (PITFL) in isolation, for example, by fixation of a posterior malleolus avulsion fracture [77]. In total, we found 13 publications recommending open repair and augmentation of the AITFL [2,11,20,28,58,77,80,98,119,135,140,167,170].

Main conclusions: The AITFL is an important stabilizer, especially for rotary stability, and even isolated injuries to the AITFL alone may lead to significant external rotary instability of the ankle mortise. Therefore, an unstable AITFL should be repaired and augmented. Bony avulsion fragments can obstruct anatomic reduction of the distal tibiofibular joint but when reduced anatomically can serve as landmarks for reduction.

#### *3.7. Role of the Posterior Malleolus*

Sir Astley Cooper, in 1822, first described fractures of the ankle with involvement of the posterior lip of the tibia [97]. The posterior lip of the distal tibia was entitled the "posterior malleolus" by Destot in 1911, and Henderson and Stuck, in 1935, suggested the term "trimalleolar" for ankle fractures involving the medial and lateral malleolus and the posterior lip of the tibia [97]. In 1922, Lounsberry and Metz discussed trimalleolar fractures as well as those with involvement of the anterior tibial lip, and they were the first to advocate open reduction and internal fixation of displaced posterior and anterior tibial fragments [97].

The posterior malleolus is affected in around 40% of ankle fractures [146]. Anatomical reduction of the articular surface and fibular notch are essential for ankle stability and functional outcomes. To address the posterior malleolus when treating ankle fractures, surgeons should choose the most adequate approach based on the fracture pattern and their own experience [3,14–17,99,146,152,154,155]. Anatomical reduction and stable fixation of the posterior malleolus are critical to improve outcomes [1,3,14–17,21,43,46,50,84,86,99,144,146,153,154].

It was Gardner who first observed, in 2006, that syndesmotic stability may be obtained more effectively by fixation of the posterior malleolus rather than by using a syndesmotic screw [50]. This observation was later confirmed by several authors [17,84,86,144].

Tosun et al. compared posterior malleolus versus syndesmotic screw fixation in trimalleolar ankle fractures. The results of this study demonstrate that posterior malleolar fracture fixation is closely related to successful radiological and functional outcomes after trimalleolar fractures. Syndesmotic screw fixation may not be needed in cases in which the posterior malleolar fracture has been fixated. For these reasons, the authors recommended that all posterior malleolar fractures have to be fixed regardless of size [144].

Furthermore, according to Verhage, the posterior fragment size is not a clear indication for its fixation [153]. A step-off, however, seems to be an important indicator for developing posttraumatic osteoarthritis and worse functional outcome [1,21,43,153]. Therefore, displaced posterior fragments involving the intra-articular surface need to be reduced and

fixated to prevent postoperative persisting step-off [153]. Furthermore, direct fixation of the posterior malleolus via an open posterolateral approach seems superior to percutaneous anterior-to-posterior fixation [15–17,84,99,154,155].

When posterior malleolus fractures occur with syndesmotic injury, anatomic fracture reduction and fixation are paramount, as they can affect syndesmotic reduction, especially with larger fragments [46]. Therefore, in any case of a displaced fracture of the posterior malleolus with a bone fragment big enough for screw or plate fixation and with an intact PITFL, the posterior malleolus should be considered the key for anatomic reduction of the syndesmosis [46]. After fixation of the posterior malleolus in an anatomic position, the further surgical steps for complete reduction and stabilization of the syndesmosis will be easy to perform. Therefore, open reduction and direct fixation of the posterior malleolus should be performed as the first step [84,97]. This surgical order has the additional advantage that fluoroscopic control of reduction quality is not limited by other implants, such as a fibular plate. In case of fixation of the posterolateral malleolus in malposition, anatomic reduction of the syndesmosis will not be possible anymore due to ligamentotaxis. Therefore, in cases where it is very difficult or even impossible to fix the posterior malleolus in an anatomic position, it might be better not to fix the posterior malleolus than to fix it in malposition.

Main conclusions: A step-off of the posterior malleolus is an important indicator for developing posttraumatic osteoarthritis and worse functional outcome. Therefore, displaced posterior malleolar fractures have to be fixed regardless of size. Fix the posterior malleolus directly from posterior whenever possible. When fixing the posterior malleolus, start with this procedure, as the posterior malleolus is the key for anatomic reduction of the syndesmosis.

As a kind of summary of our investigations, we formulated the following principles for the surgical treatment of unstable syndesmotic injuries, which can be considered supported by varying degrees of evidence in literature:

*3.8. Recommended Principles for the Surgical Treatment of Unstable Syndesmotic Injuries*

These recommended main principles for the surgical treatment of unstable syndesmotic injuries were fused into the following evidence-based surgical treatment algorithm (Figure 1). Practicability of this algorithm is additionally based on the clinical experience of the first author (M.R.), who has performed more than 300 flexible dynamic syndesmotic stabilizations using an *Internal*BraceTM since 16 December 2013. Corresponding clinical and radiological outcome studies are currently running.

(**A**)

**Figure 1.** *Cont*.

(**B**)

**Figure 1.** *Cont*.

(**C**)

**Figure 1.** *Cont*.

#### (**D**)

**Figure 1.** (**A**) Evidence-based surgical treatment algorithm for unstable syndesmotic injuries. (**B**) Evidence-based surgical treatment algorithm for unstable syndesmotic injuries. Exemplary treatment path for grade 1 injuries. (**C**) Evidence-based surgical treatment algorithm for unstable syndesmotic injuries. Exemplary treatment path for grade 2 injuries. (**D**) Evidence-based surgical treatment algorithm for unstable syndesmotic injuries. Exemplary treatment path for grade 3 injuries.

#### *3.9. Evidence-Based Surgical Treatment Algorithm for Unstable Syndesmotic Injuries*

For the first decision before starting surgery, the surgeon has to evaluate if there is a displaced posterior malleolar fragment amenable to open anatomic reduction and direct fixation with a lag screw or an anti-glide plate (Figure 1A). If so, this procedure should be performed as the first step of surgery due to the following three reasons: (1) direct fixation provides excellent primary stability of the posterior syndesmosis. (2) After anatomic reduction and direct fixation of the posterolateral malleolus, the following surgical steps will be quite easy to perform. (3) Fluoroscopic control of reduction quality is not limited by other implants like a fibular plate.

The next step after direct fixation of the posterior malleolus, or the first step in case of an intact posterior malleolus, is direct visualization of the AITFL and an intraoperative grading of the injury pattern under direct view (Figure 2). The surgeon should be aware that only grade 3 injuries would be detected by the well-known Cotton test or its hook test modifications [22,90,101,103]. Increased external rotation and posterior sagittal translation indicates an isolated tear or bony avulsion of the AITFL, representing a grade 1 injury (Figure 2A); increased anterior sagittal translation indicates an additional tear or bony avulsion of the PITFL, representing a grade 2 injury (Figure 2B); and increased lateral translation indicates additional medial instability, representing a grade 3 injury (Figure 2C). Further treatment strategy should be according to the detected individual injury pattern:

We have already exemplified in detail how to perform these stabilization techniques in 2017 [119]. In our experience, the most common procedure is anterior stabilization with an *Internal*BraceTM, either as single anterior stabilization or as double stabilization in combination with direct refixation of the posterior malleolus or a slightly posteriorly directed suture-button device in order to indirectly stabilize an injured PITFL. As a promising alternative to an indirect posterior stabilization by use of a suture-button device, recently, some surgeons have also been performing a direct stabilization of the PITFL with an additional *Internal*BraceTM to an increasing degree. However, to the best of our knowledge, this technique has only been described in a cadaver model so far [119]. Triple stabilization by use of an additional central suture-button device or a syndesmotic screw proximal of the incisura is rarely necessary in our hands. As a suture-button-device, we have used the knotless syndesmotic TightRope® implant system provided by Arthrex in our own cases, as this implant, to the best of our knowledge, represents the most frequently used and most investigated suture-button-device. However, alternative implant systems provided by other manufacturers are currently available as well.

A clinical example of a single anterior stabilization in a type B ankle fracture with displaced bony tibial avulsion of the AITFL (Figure 3A) is shown in Figure 3. After secure radiological and clinical exclusion of any unstable injury to the PITFL or the posterior malleolus, the distal fibular fracture was fixed with a special anatomically shaped titanium distal fibular plate with eyelets for tape augmentation of the AITFL and PITFL (Arthrex, Naples, FL, USA). The bony AITFL avulsion fragment was anatomically reduced under direct visualization and fixed with a 3.5-mm headless compression screw (Figure 3B). Due to its size, the bony fragment was not amenable to fixation with a stronger screw. Therefore, a FiberTape® (Arthrex, Naples, FL, USA) for augmentation of the AITFL was pulled through the anterior eyelets of the plate (Figure 3C) and fixed to the distal tibia exactly in line with the course of the uninjured AITFL with a 4.75-mm SwiveLock® (Arthrex, Naples, FL, USA). Figure 3 D shows the final result after osteosynthesis of the distal fibula with a titanium plate, refixation of the bony avulsion fragment with a compression screw, and augmentation of the AITFL with an *Internal*BraceTM (Arthrex, Naples, FL, USA).

(**A**)

(**B**)

#### (**C**)

**Figure 2.** (**A**) Intraoperative assessment of a grade 1 injury. (**B**) Intraoperative assessment of a grade 2 injury. (**C**) Intraoperative assessment of a grade 3 injury.

(**A**)

(**B**)

**Figure 3.** *Cont*.

(**C**)

(**D**)

**Figure 3.** (**A**) Type B ankle fracture with displaced tibial bony avulsion of the AITFL. (**B**) Type B ankle fracture with displaced bony avulsion of the AITFL. The distal fibular fracture was fixed with a special anatomically shaped titanium distal fibular plate with eyelets for tape augmentation of the AITFL and PITFL (Arthrex, Naples, FL, USA). The bony AITFL avulsion fragment was anatomically reduced and fixed with a 3.5-mm headless compression screw. (**C**) Type B ankle fracture with displaced bony avulsion of the AITFL. A FiberTape® (Arthrex, Naples, FL, USA) for augmentation of the AITFL has been pulled through the anterior eyelets of the plate and fixed to the distal tibia with a 4.75-mm SwiveLock® (Arthrex, Naples, FL, USA). (**D**) Type B ankle fracture with displaced bony avulsion of the AITFL. Final result after osteosynthesis of the distal fibula with a titanium plate, refixation of the bony avulsion fragment with a compression screw, and augmentation of the AITFL with an *Internal*BraceTM (Arthrex, Naples, FL, USA).

#### **4. Discussion**

Our aim was to provide the currently best available evidence for surgical treatment of unstable syndesmotic injuries. Therefore, we searched PubMed, Embase, Google Scholar, The Cochrane Database of Systematic Reviews, and the reference lists of systematic reviews of relevant studies dealing with the surgical treatment of unstable syndesmotic injuries. Then we tried to draw important conclusions from the pertinent literature concerning surgical treatment of unstable syndesmotic injuries, to transform these conclusions into surgical principles supported by the literature, and finally to fuse these principles into an evidence-based surgical treatment algorithm. In our hands, this surgical treatment algorithm has been working well for more than seven years now.

A total of 171 articles were analyzed, and to summarize our results, we found the following main principles for surgical treatment of unstable syndesmotic injuries: (1) anatomic reduction is crucial for the long-term results; (2) open reduction by direct visualization is strongly recommended; (3) repair what is injured; (4) bony avulsion fragments must be identified and reduced and can serve as landmarks for anatomic reduction; (5) the use of reduction clamps or forceps should be avoided whenever possible; (6) fix the posterolateral malleolus directly from posterior whenever possible; (7) when fixing the posterolateral malleolus, start with this procedure; (8) the AITFL is an important stabilizer especially for rotational stability; (9) an unstable AITFL should be repaired and augmented; (10) use flexible dynamic stabilization techniques whenever possible; and (11) use syndesmotic screws only as a salvage procedure.

However, there are some limitations to our study. Our study was not a systematic review designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and study quality of the cited references was not assessed based on any quality appraisal scales. Moreover, due to our language selection criteria, there might be additional important studies not considered in our work.

Furthermore, our aim was to develop the best available solution for unstable syndesmotic injuries with regard to medical and not economic issues, and we are aware of the fact that our approach for treating unstable syndesmotic injuries is quite expensive compared to the simple and cheap syndesmotic screws, for example [115]. However, regarding the well-known severe consequences of failed syndesmotic repairs, we strongly recommend treating unstable syndesmotic injuries using the best implants available. In the long run, it does not seem reasonable to save money in the primary care for unstable syndesmotic injuries because the consequence might be very high costs for the treatment of ankle osteoarthritis.

#### **5. Conclusions**

Current literature provides sufficient arguments for the development of an evidencebased surgical treatment algorithm for unstable syndesmotic injuries. Anatomic reduction is crucial to prevent posttraumatic osteoarthritis. Therefore, flexible dynamic stabilization techniques should be preferred whenever possible. An unstable AITFL should be repaired and augmented, as it represents an important stabilizer of external rotation of the distal fibula.

**Author Contributions:** Conceptualization, M.R.; methodology, M.R. and C.E.; investigation, M.R. and C.E.; resources, M.R., G.M. and O.N.; data curation, M.R. and O.N.; writing—original draft preparation, M.R.; writing—review and editing, G.M., O.N., W.B. and C.E.; visualization, M.R. and C.E.; supervision, W.B. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** In these extraordinary times, we would like to thank the medical staff all around the world for fighting against the COVID-19 pandemic.

**Conflicts of Interest:** Markus Regauer and Gordon Mackay are paid consultants of and receive royalties from Arthrex (Naples, FL, USA). The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The remaining authors declare no conflict of interest.

#### **References**

#### *Article*

### **Can a Single Trial of a Thoracolumbar Myofascial Release Technique Reduce Pain and Disability in Chronic Low Back Pain? A Randomized Balanced Crossover Study**

**Luana Rocha Paulo 1,2,3, Ana Cristina Rodrigues Lacerda 1,4, Fábio Luiz Mendonça Martins 1,4, José Sebastião Cunha Fernandes 4, Leonardo Sette Vieira 2, Cristiano Queiroz Guimarães 2, Sílvia de Simoni Guedes Ballesteros 2, Marco Túlio Saldanha dos Anjos 5, Patrícia Aparecida Tavares 3, Sueli Ferreira da Fonseca 4, Murilo Xavier Oliveira 1,4, Mário Bernardo-Filho 6, Danúbia da Cunha de Sá-Caputo 6, Vanessa Amaral Mendonça 1,4 and Redha Taiar 7,\***

**Abstract:** Although manual therapy for pain relief has been used as an adjunct in treatments for chronic low back pain (CLBP), there is still the belief that a single session of myofascial release would be effective. This study was a crossover clinical trial aimed to investigate whether a single session of a specific myofascial release technique reduces pain and disability in subjects with CLBP. 41 participants over 18 years old were randomly enrolled into 3 situations in a balanced and crossover manner: experimental, placebo, and control. The subjects underwent a single session of myofascial release on thoracolumbar fascia and the results were compared with the control and placebo groups.  There were no effects betweentests, within-tests, nor for interaction of all the outcomes, i.e., NPRS (η <sup>2</sup> = 0.32, F = 0.48, *p* = 0.61), PPT (η<sup>2</sup> = 0.73, F = 2.80, *p* = 0.06), ODI (η<sup>2</sup> = 0.02, F = 0.02, *p* = 0.97). A single trial of a thoracolumbar myofascial release technique was not enough to reduce pain intensity and disability in subjects with CLBP.

**Keywords:** fascia; chronic low back pain; myofascial release

#### **1. Introduction**

Chronic non-specific low back pain (CLBP) is a condition characterized by pain, stiffness, and/or muscular tension [1] and is an important health problem throughout the world [2]. In CLBP, pain processing and modulation by the central nervous system may be altered. Manual therapy (MT) is a conservative intervention for treatment of

**Citation:** Paulo, L.R.; Lacerda,

A.C.R.; Martins, F.L.M.; Fernandes, J.S.C.; Vieira, L.S.; Guimarães, C.Q.; Ballesteros, S.d.S.G.; Anjos, M.T.S.d.; Tavares, P.A.; Fonseca, S.F.d.; et al. Can a Single Trial of a Thoracolumbar Myofascial Release Technique Reduce Pain and Disability in Chronic Low Back Pain? A Randomized Balanced Crossover Study. *J. Clin. Med.* **2021**, *10*, 2006. https://doi.org/10.3390/ jcm10092006

Academic Editors: Władysław Jagiełło and Marco Alessandro Minetto

Received: 26 March 2021 Accepted: 30 April 2021 Published: 7 May 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

CLBP [1,3,4]. Myofascial release is a form of MT, which involves the application of lowload and long-duration stretches to the myofascial complex. Although the mechanisms of action and effectiveness in individuals with CLBP are still unclear, myofascial release techniques are widely used by physical therapists in the management of CLBP, with the intent to restore the optimal length of the fasciae tissue, decrease pain intensity, and improve functionality [1,4–9]. Previous reports point to the effects of stabilization or global physical exercise in pain relief in subjects with CLBP with few studies for manual techniques alone or as an adjunct therapy [10–14].

Considering that previous studies recommended the adoption of interventions focused on the soft-tissues for the management of CLBP, there is still the belief among clinicians that an isolated session of MT, e.g., myofascial release, is effective in reducing pain intensity and disability [9,15]. As far as we know, only one study investigated the effects of an isolated myofascial release protocol on pain intensity and disability in patients with CLBP. Although the authors did not show clearly whether the improvement in pain intensity and disability was clinically relevant, they suggested the myofascial protocol that was used reduced these outcomes [4]. In this investigation, one of the areas chosen for intervention was the thoracolumbar fascia (TLF), which contains a great proportion of post-ganglionic sympathetic fibers and is densely innervated by free nerve endings, as low-thresholdmechanosensitive C fibers, which are responsive to MT [5,16] with repeated mechanical or biochemical stimulation.

The anatomical distribution of TLF layers, the aforementioned specificities of this tissue, and the support of the literature on the potential nociceptive function of TLF in the etiology of low back pain [17], allow for the inference that active movement of the trunk, such as flexion-extension, will increase the shear of the tissue and contribute to pain reduction and function [7,18–25]. Therefore, the present study aimed to verify if there is an immediate effect of a specific myofascial release technique on the TLF of individuals with CLBP, measured by pain intensity and disability, in comparison with that of control and placebo situations [23,25].

#### **2. Materials and Methods**

#### *2.1. Study Design*

This was a crossover open clinical trial performed between February and June 2019. The trial was registered with the Clinical Trials Government Identifier (ReBEC—reference number 8197). The current study conformed to the Consolidated Standards of Reporting Trials statement for reporting clinical trial studies. All subjects provided written informed consent to participate in this study, which was conducted in accordance with ethical principles for research involving humans (principles of the Declaration of Helsinki) and received approval from the Ethics and Research Committee of the Federal University of Jequitinhonha and Mucuri Valleys (reference number 3.435.537).

All the participants underwent three situations in a randomized and balanced order. The sequence of situations was randomized using a website (www.random.org, accessed on 8 July 2019). A familiarization with the experimental procedures was performed, followed by anamnesis (age, sex, and level of physical activity) and evaluation of the prognosis or risk profile using the STarT Back Screening Tool (SBST) questionnaire, which consists of nine items divided into physical and psychosocial subscales [26].

#### *2.2. Study Populations*

Subjects were recruited in the city of Diamantina, Minas Gerais, Brazil. Inclusion requirements and eligibility were men and women over 18 years old, with a medical diagnosis of CLBP or low back pain for more than 3 months, who obtained a minimum cut-off value of 2 points of pain by the Numerical Pain Rating Scale (NPRS) during data collection. Exclusion criteria were previous or scheduled surgeries in the torso or limbs; those with suspicion of severe fractures or pathologies (tumor, inflammation, infection, rheumatological disorder, aortic aneurysm); diagnosis of radiculopathy or neuropathy

(with or without spinal canal stenosis with proof of magnetic resonance imaging—MRI); structural deformity in the spinal column; spondyloarthropathy, disabling pain and physical disability that would make it impossible to perform the study procedures; use of painkillers or anti-inflammatory medicines 48 h before the first test phase or during the study; neurological or psychiatric disorder; and presence or suspicion of pregnancy. In addition, the subjects that self-reported physical activity levels equal to or greater than those recommended by the American College of Sports Medicine (ACSM) were excluded [27–29].

#### *2.3. Sample Size Calculation*

The sample size was estimated by the GPower® program (Franz Faul, Universität Kiel, Kiel, Germany), version <IP_ADDRESS>. For this, we used a priori analysis, with ANOVA for comparisons between groups for the variable NPRS [30]. The effect size was calculated from the difference in the means with standard deviation within each group of 0.9. Thus, considering an effect size of 0.42, power of 0.80%, and alpha error 5%, the sample size was estimated at 41 volunteers. There were no withdrawals, so there was no need to analyze the data with the intention to treat.

A total of 52 subjects agreed to participate, of them, 10 individuals gave up or did not attend the test site on the scheduled date and 1 individual did not meet the described inclusion criteria. Therefore, 41 subjects participated in all stages of the research (Figure 1). Of the 41 individuals, 61% were women and 56% declared themselves sedentary. In addition, the median age was 36 years and the self-reported pain averaged 3.4 to 3.7 points. Among the subjects, 56% were classified in terms of poor prognosis in the SBST as low risk (Table 1).

**Table 1.** Characteristics of the participants at baseline.

\* CI: confidence interval; <sup>1</sup> NRPS: visual numeric pain scale; <sup>2</sup> PPT: pain pressure threshold; <sup>3</sup> FTF: fingertip-tofloor; <sup>4</sup> SBST: STarT Back Screening Tool.

#### *2.4. Outcome Measures*

The measurements of pain were the primary outcome. We used the Pressure Pain Threshold (PPT) and NPRS as the instruments to measure pain. As a secondary outcome, the Oswestry Disability Index questionnaire (ODI—version 2.0, Department of Nursing, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil) evaluated the prognosis and functionality of the subjects. All analyses were performed to compare the results before (pre-test) and immediately after (follow-up) each experimental situation.

**Figure 1.** Flow of participants throughout in all stages of the research.

For pain measurements, the NPRS was used to quantify the intensity of pain in all areas of the study, ranging from 0 to 10, with 0 classified as no pain and 10 as the worst pain imaginable. This instrument is proven to be a competing and valid predictor of pain intensity [31]. The pain threshold was assessed using a PPT device (FDX Series Force Gage, Wagner Instruments, Greenwich, CT, USA), with a graduation capacity of 50 × 0.05 lbf, <sup>800</sup> × 0.5 ozf, <sup>25</sup> × 0.02 kgf and 250 × 0.2 N, and a 1 cm<sup>2</sup> plunger connected to a mechanical force gauge that indicates the pressure applied at the marked location. The plunger of the device was positioned perpendicularly to the paravertebral muscles, respecting the proximity of 2 cm laterally to the midline between the L3–L4 spinous process. The pressure was applied progressively and perpendicular to the skin, with an average of 1 kg/cm2/s, until the volunteer signaled the onset of pain or discomfort. After signaling, the device was removed from contact with the individual's body and the Newton's quantification was noted [32,33]. Initially, a familiarization was performed on the anterior muscles of the forearm. For the assessment, after the participants were positioned for the interventions, the point for assessed was marked with a pen and three measurements were taken at the same site (pre-test and follow-up), with a 30 s interval between them. The mean of the three measurements was used for analysis [1,34].

The ODI Version 2.0 questionnaire [35] was used to quantify the disability caused by low back pain in daily activities. Scores were given from 0% (no dysfunction; independence) to 100% (lowest level of functionality; total dependence), divided into 5 levels, where the first described no limitation and the others described limitation or inability to function. The total score is the percentage value calculated by the following equation: Total score = (Σ item score/50) × 100. With all 10 questions answered, the total score was divided by 50 (10 × 5). The published minimally clinically important difference (MCID) values for ODI is 12.88 (sensitivity 88%, specificity 85%) [36]. It must be taken into consideration that the ODI is a questionnaire with a one-dimensional factorial structure. Important psychometric properties and internal consistency, and their ability to measure functional limitations were considered to be very accurate according to the actual level of severity of the dysfunction experienced by the assessed subjects [37].

#### *2.5. Intervention*

Forty-one of the fifty-two volunteers were selected after the initial screening and exclusion through the eligibility criteria. All were enrolled in the three situations: (1) control (C), (2) experimental (Exp), and (3) placebo (Plac). In our work, a single trained and experienced therapist, a member of the Brazilian Academy of Fasciae (ABSFascias), applied the technique in all situations. Due to the design of our study, only the assessor was blinded. However, all the subjects performed the three situations on consecutive days respecting a minimum interval of 24 h in order to minimize the potential bias due to the high level of adaptability of the connective tissue [3].

#### 2.5.1. Control

The subjects were instructed to remain in the supine position for five minutes on a stretcher to minimize the effects of tension forces or stimuli on the tissue, without making movements, to mimic the time spent in the act of performing the intervention.

#### 2.5.2. Experimental

The subjects underwent a single session of the new approach to be tested to release the TLF in a sedestation position with feet supported and the thoracolumbar region properly undressed. The trunk flexion goniometry of each participant was performed and the value of 30◦ was marked with a barrier to limit the necessary movement during the technique. The trained researcher positioned their hands on all participants without sliding over the skin or forcing the tissue, with the cranial hand close to the last rib and at the T12–L1 level on the right side of the individual's body and the caudal hand on the ipsilateral side between the iliac crest and the sacrum. Then, the researcher caused a slight traction in the

tissues by moving their hands away from each other in a longitudinal direction. Then, the participant was instructed to perform five repetitions of active trunk flexion-extension (30◦), while the researcher followed the movement with both hands simultaneously positioned, without losing the initial tissue traction and position (Figure 2). The same technique and the same number of repetitions of active trunk flexion-extension were repeated with the researcher's hands positioned on the opposite sides. This technique lasted approximately five minutes [3,38,39].

**Figure 2.** (**A**) Trunk position (90◦) and researcher's hands contact at the beginning of the technique. (**B**) 30◦ trunk flexion and researcher's hands contact at the end of the technique.

#### 2.5.3. Placebo

The subjects were not submitted to the technique of manual thoracolumbar fascia release, but they slowly performed ten repetitions of active trunk flexion-extension (30◦) in the same position as the experimental situation. Due to the fact that touch can provide not only well-recognized discriminative input to the brain, but also an affective input, there was no touch from the researcher at this stage [16].