Comparison of whole-body vibration training, strength training and health education on physical function and neuromuscular function of individuals with knee osteoarthritis: a randomized clinical trial

Background Knee osteoarthritis (KOA) is one of the leading causes of global disability which causes knee pain, sti ﬀ ness, and swelling. Impaired neuromuscular function contributes to the development and/or progression of KOA. As a new modality to treat KOA, whole-body vibration (WBV) training is considered to improve pain and physical function effectively. However, limited numbers of studies were designed to investigate the effect of WBV on neuromuscular function in KOA. Methods 81 eligible participants with KOA were randomly allocated to WBV, strength training (ST) and health education (HE) groups. Each group of participants was encouraged to perform the WBV training, similar strength training and health education program, respectively. These supervised interventions were performed three times per week for 8 consecutive weeks. Neuromuscular function was measured with isokinetic muscle strength and proprioception. Physical function was assessed with Timed Up and Go (TUG) and 6-min Walk Distance tests. Results Physical function and neuromuscular function did not show signi�cant difference between three groups (p > 0.05). However, post-hoc test showed that isokinetic knee muscle strength of WBV group (peak torque of extensor at 180°/s, peak torque of �exors at 180°/s, peak work of extensor at 180°/s, and peak work of �exor at 90°/s, all p < 0.05) increased signi�cantly compared with HE group. Similarly, compared with ST group, muscle strength of WBV group (peak torque of extensor at 180°/s and peak work of extensor at 180°/s, p < 0.05) improved signi�cantly. Conclusion The current study showed that the advantage of WBV training on muscle strength gain in patients with KOA compared with similar strength training without vibration and health education.


Background
Knee osteoarthritis (KOA) is a degenerative, non-infectious knee joint disease and one of the leading causes of global disability [(1)].Patients with KOA often suffer from arthralgia, stiffness, swelling, decreased muscle strength, impaired proprioceptive function and physical foundational limitation [ (2)(3)(4)].In US, it was reported that the prevalence of KOA has increased to 33.6%, thereby affecting most adults aged 65 years old and above [(5)].Considering the improving longevity and the increasing prevalence of obesity and joint injury, the prevalence of KOA may continue to increase in future decades; therefore, there is an increasing need to address KOA.
As far as we know, no cure for KOA exists.As suggested by several international guidelines, nonpharmacological and pharmacological modalities (even surgical treatment) should be combined to manage KOA [(6-8)].Among these treatments, exercise is recommended for effective treatment; examples of exercises are aerobic and/or resistance land-based exercise, aquatic exercise, and Tai Chi [(6)].
Strength exercises are considered as the foundation of non-pharmacological treatments [(9)].
Several studies have shown that the impaired neuromuscular function, such as proprioception and muscle strength of the affected knee joint, might play a detrimental role in KOA [ (4,10,11) ].The weakness of muscle strength around the knee would contribute to joint instability, which would change the alignment and stress of the knee, thereby accelerating knee OA progression [(12)].Meanwhile, the proprioception of the affected joint has been reportedly impaired signi cantly in KOA compared with the age-matched controls [(4)] even compared with the non-symptomatic knee [(13)].
With the lower load on the affected joint, whole-body vibration (WBV) training was proposed as an effective and potentially feasible neuromuscular modality to treat several musculoskeletal system diseases, such as low back pain, osteoporosis and chronic achilles tendonitis [ (14,15)] even in patients with neurological disorders [(16)].
Recently, treatment of KOA has been evaluated, particularly in the aspects of pain relief and physical function improvement [(17-19)].Several systematic reviews and meta-analyses a rmed the therapeutic effects of WBV training on pain and function in individuals with KOA [ (20,21)].
However, limited studies have evaluated the effect of WBV training on neuromuscular function in individuals with KOA, which was associated with symptoms, prevalence and progression.Segal et al.
[ (22)] conducted a randomised controlled study to determine the effect of exercise on the vibration platform on proprioception, muscle strength and power in the women with KOA risk factors.However, there was no signi cant improvement in the outcome measures compared to the matched exercise group

Methods
This study was a single-centre, single-blind randomised controlled trial with blinded outcome assessment, which was conducted at the Sport Medicine and Rehabilitation Centre, Shanghai University of Sport.It was approved by the Ethics Committee of the Shanghai University of Sport (Ref.No.: 2016-016) and registered at Chinese Clinical Trial Registry a priori as a clinical trial (ID: ChiCTR-IOR-16009234).In addition, this study adhered to CONSORT guidelines.

Participants
With settings of α = 0.05, power (1 − β) = 0.80 and effect size = 0.25, power analysis showed that three groups of 81 participants in total were the required sample size.The effect size (0.25) of the extensors' peak torque was used to estimate the sample size.Considering the progression of disease and drop-out, 30 subjects in each group were recruited for this study.
The voluntary participation of KOA patients was requested via posters on community centres in Yangpu District, Shanghai, China from July 2017 to September 2018.The diagnosis of KOA was performed by an orthopaedic surgeon based on the patients' medical history, X-ray imaging and physical assessment.Based on the classi cation criteria of the American Rheumatism Association for KOA [( 27)], the inclusion criteria were as follows: (1) men or women with radiographic diagnostic criteria of de nite KOA (unilateral or bilateral) and who reported pain symptoms for at least 3 months; (2) mild-to-moderate KOA (Lequesne Knee Score = 1to 7); (3) aged 50-70 years old; (4) medication not expected to change during the study period; and (5) available three times a week for over 3 months.The exclusion criteria were as follows: (1) had undergone knee surgery in the past 6 months; (2) had acute symptomatic KOA; (3) had muscular, joint or neurological conditions that affect lower limb function; (4) underwent a structured exercise program speci cally for KOA; (5) unable to understand the study's procedure; and (6) had motor neuron disorders, such as Alzheimer's and Parkinson's diseases [(19)].The research designer (LZ) took charge of contacting the eligible participants, con rming their willingness to complete the trial and arranging the baseline assessment of outcomes.
After screening, 81 eligible participants were informed about the study procedures and given written informed consent before enrolled in the study.These participants were randomly divided into WBV, strength training (ST) and health education (HE) groups using computer-generated randomisation by the main research designer (WL).The group randomisation was separated into opaque envelopes which was kept by the main research designer (WL).

Outcome measures
All outcome assessments were conducted by the independent research assessor who was blind with group allocation at pre-intervention and post-intervention.For the bilateral KOA, the affected side was de ned as the worse side.
Before the intervention, the demographic questionnaire was collected, including participants characteristics (sex, age, Body Mass Index, Lequesne Knee Score and affected side).After intervention, all participants were requested to return to the laboratory within 2 days and complete the post-intervention assessment.

Isokinetic muscle strength
Knee extensor and exor strength of the affected side were measured using an isokinetic dynamometer (Physiomed, CON-TREX, TP 1000, Germany).Before the formal test, the participants were informed about the test procedure and performed a 5 min warm-up.At rst, the assessor secured them to the dynamometer at the upper chest, pelvis and distal femur on the tested side with straps.Then, the participants were instructed to familiarise themselves with the procedure through three submaximal contractions.In the formal test, the maximal concentric knee extension-exion contractions were performed at angular velocities of 90°/s and 180°/s.The work of each trial was recorded from 80° to 10°o f the knee moving angle, and 0° was considered as the full extension.During the test, the assessor verbally encouraged participants to move as forcefully as possible.The peak torque and peak work (PT and PW; Nm/kg and W/kg, respectively) normalised by body mass were recorded for analysis.This study performed strength training focused on the knee extensors.Therefore, the peak torque of knee extensor was considered as the main outcome of muscle strength which was powered for sample size.

Proprioception of knee
The proprioception of knee was observed as the threshold for the detection of passive movement (TDPM) and was measured using a reliable method [(28)].The participants were informed about the proprioception test procedure.In a sound-attenuated room, the participants were isolated to reduce any auditory or visual interference.TDPM was tested using an electrically driven movable frame.The participants were instructed to sat on an adjustable chair, which helped them place foot lightly on the plane.During the test, the plane moved the shank forward or backward at a velocity of 0.4º/s.The angle of the knee joint was adjusted to 120º by a goniometer.The patients would press the handheld stop button immediately when they perceived the movement of the knee, then report the direction.The rotation angles of the frame were determined as the threshold for the detection of exion and extension.The mean value of three successful trials in each direction was used for analysis.

Self-reported knee pain
The 10 cm visual analogue scale (VAS) was used to assess the knee pain of the affected side over the last week.The number 0 indicated no pain, whereas 10 represented maximal pain.

Physical function
The Timed Up and Go test (TUG) and the 6-min Walking Distance test (6MWD) were administered to determine the function performance of participants.These methods are simple and reliable measurements which have been used in previous studies on KOA [(19, 29)].In the TUG test, the participants were requested to perform the following tasks on optimal speed to the best of their ability.they were instructed to stand up from a standard chair (40 cm height), walk 3 m, turn around, walk back to the chair and sit down., the completion time was measures by a chronograph in second.The total test was timed by a chronograph (in seconds).As for 6WMD, the participants were asked to walk for 6 min, and the distances were recorded.All participants must nish these tests thrice for the average values to be calculated.

Intervention
The same certi ed physical therapist supervised the interventions in the WBV, ST and HE group.Each training session comprised a 5 min warm-up and 5 min cool-down in WBV and ST.

Whole-body vibration training
Participants in the WBV group performed the training 3 days per week for 8 weeks.WBV training was conducted on a vibration device (i-vib5050; Sport Platform, China).During the training, the participants performed static squat barefoot on the platform with bent knee (30º and 60º).The distance between their feet was consistent with the shoulders.the physical therapist adjusted the angle of knee exion throughout each session, timed the duration time and prevented the participants from falling.As showed in Table 1, the duration time, sets and total time were increased progressively over the 8-week training period.The parameters of WBV were set at the frequency of 20 Hz and amplitude of 2 mm.

Strength training
The ST group undertook three training sessions per week for 8 weeks the same as the WBV group.Likewise, all sessions were under the supervision of the same physical therapist in the WBV group.However, the participants performed static squat on at ground.The protocol of ST, including the duration time and the angle of the bent knee, was parallel with WBV except for the vibration exposure (Table 1).

Health education
The participants in the HE group received 8 weeks of health education.They attended one 60-min group session per week.Each session consisted of a 30-min lecture and a 30-min discussion.The session was facilitated by the same physical therapist in the WBV and ST groups.The lectures were focused on health-related topics, such as OA, aging and nutrition.Furthermore, the participants in the HE group were required to maintain their previous lifestyle and not to attend any other regular rehabilitation programs during the study period.

Statistical analysis
The SPSS statistical software program (IBM, Chicago, IL, USA) was used for statistical analysis.The data were included for analysis of all participants and Intention-To-Treat (ITT) analysis was be utilized.All data were expressed as means ± SD.To evaluate the normality of these data, the Shapiro-Wilk test was used.The one-way analysis of variance (ANOVA) and the chi-squared test were performed to determine the difference of demographic characteristics among the WBV, ST and HE groups.Then, the two-way repeated measurements ANOVA was used to determine the difference in outcomes among the three groups.The effect size of between-group effect was calculated by partial eta-square.For post hoc test, the difference of each index relative to baseline was calculated, and the one-way repeated measurements ANOVA was used for pairwise comparison.Signi cance was set at p < 0.05.

Participation
In this study, 81 participants were included for data analysis with 27 in each group.In addition, there were 17 participants dropped out the interventions (5 in WBV group, 4 in ST group, and 8 in HE group).Furthermore, the main reasons for leaving were: 1) loss of interest; 2) long distance to the rehabilitation centre; 3) other diseases not related to intervention in this study.
The demographic characteristics of the participants are shown in Table 2.There was no signi cant difference among these three groups regarding demographic and anthropometric data, such as age, gender, height, weight and Body Mass Index (BMI).No signi cant differences were found in the data collected prior to intervention between groups, thereby con rming the baseline homogeneity of these groups.

Isokinetic muscle strength
Isokinetic strength of knee extensor and exor were measured at the angular velocities of 90°/s and 180°/s.As shown in Fig. 1 and Table 3, no signi cant main effect of these variables among three groups was found (p > 0.05).Furthermore, at 90°/s, a signi cant interaction effect in peak work of knee exors of three different groups was found (p < 0.05, η2 = 0.09).After the post hoc test, the peak work of knee exors signi cantly improved in WBV group compared with HE group (p < 0.05, 95% = 0.02 -0.42).

Proprioception of knee
Fig. 3 and Table 4 shows the differences in TDPMs of knee exion and extension in three groups.
Regarding the proprioception of knee joint, no signi cant change was found on exion and extension among HE, ST and WBV groups (p > 0.05).

Self-reported knee pain and physical function
As illustrated in Table 4, there was no signi cant difference in the pain relief and function improvement caused by WBV, ST and HE (p > 0.05).

Discussion
Along with pain and stiffness, patients with KOA experienced decreased muscle strength, impaired neuromuscular function and limited physical function [ (30)].As a type of strength exercise, WBV training has been proposed for the treatment of KOA.However, several systematic reviews about the effect of WBV for KOA were explored, thereby leading to dispersed results [ (20,21,31,32)].These studies failed to indicate the superiority of WBV compared with a control group or a similar strength training group.Thus, this study attempted to determine the effects of 8-week WBV training on pain, physical function and neuromuscular function in individuals with KOA.
In this study, the participants were randomly assigned to WBV, ST, and HE group and performed corresponding intervention for 8 weeks.The results showed that the 8-week WBV training effectively increased isokinetic strength of knee extensors compared with ST or HE, while these three interventions didn't promote the knee passive motion sense.As for the self-reported pain intensity and physical function, WBV, ST, and HE led to a similar effect in these clinical outcomes, although the pain and the time of TUG test improved signi cantly after 8 weeks of all three interventions.Generally speaking, the nding of this study demonstrated that compared with similar training and health education, whole body vibration intervention could signi cantly promote the increment in knee extensors strength and have a similar effect on knee pain relief and physical function improvement.

Muscle strength
The main nding of this study is the signi cant improvement in muscle strength (park torque and peak work) in the WBV group compared with similar strength training.As reported in previous studies, the improvements in muscle strength and power might be the results of several neural factors [(33)] and biochemical factors [(34)].Several factors were speculated to be involved in the possible mechanism underlying the effect of WBV training on strength gains, such as increased recruitment, synchronisation, muscular coordination and proprioception [( 30)].However, the results of proprioception in our study showed that the WBV training did not promote the improvement of proprioception.Considering the lack of electromyography data, whether the recruitment, synchronisation and coordination of the muscles around knee joint were enhanced after 8 weeks of WBV training cannot be con rmed.
There are several reasons that can explain the increased effect of training on muscle strength.Firstly, during vibration training, the length of the muscle-tendon complex in skeletal muscle changed, and vibration elicited the "tonic vibration re ex," which is one kind of muscle response produced by the activation of muscle spindles, mediation of a afferents and activation of muscle bres [( 23)].Furthermore, during the ST, the force depended on the mass and the gravity acceleration.However, for the participants in the WBV group, the acceleration was changed by platform's vibration, which adjusted the resistance during training sessions.Another possibility might be that the WBV training stimulated growth hormone secretion, which was bene cial to the gain of muscle strength.
Currently, there is no consensus on the effect of WBV training on muscle strength in patients with KOA [(18, 23, 35, 36)].Several researchers have a rmed the advantage of WBV training on muscle strength in KOA, which was consistent with our result [ (24,25,36)].Due to the absence of guidelines for optimal protocol, previous studies employed different parameters, such as frequency, amplitude, duration, posture of WBV training, and even the vibration device.As mentioned previously, mechanical vibrations provoke a re exive muscle contraction, which is referred to as tonic vibration re ex [(37)].The magnitude of provoked tonic vibration re ex is related to vibration frequency, vibration displacement, initial position applied in WBV training, vibration type and the training protocol [(38)].The difference between these parameters employed might be responsible for the inconsistent conclusions.

Proprioception
It has been generally accepted that impaired knee proprioception played an important role in the onset and progression of KOA as a local factor [ (4,39)].Compared with age-matched healthy controls, the patients with KOA showed signi cant impairment in position sense or motion sense [(40, 41)].WBV exposure is a neuromuscular training in the management of several neurological disorders and musculoskeletal disease.It was speculated that WBV training could help improve muscle strength and proprioception and neuromuscular responses [(42)].However, the result of our study showed that WBV training did not improve proprioception in participants with KOA.Currently, limited studies have been designed to investigate the effect of WBV training on proprioception in KOA.Trans et al. [(24)] compared the effects of two different vibration trainings on KOA and found that the TDPM was improved in WBV in the balance-vibration group but not in the conventional stable-vibration group.The stable WBV device (vertical platform) was applied to this study, and the difference in the device might have contributed to the ineffectiveness in proprioception.Segal collected the vibration perception threshold of the lower extremities [( 22)], and similar to our experiment, positive results were not found.

Pain
Compared with the baseline, the knee pain decreased signi cantly in the HE and WBV groups, and knee relief tendency was found in the ST group, although no signi cant intergroup effect was found.The results of the pain state are consistent with those in previous studies.For example, in Tsuji's study [( 17)], the participants with knee pain underwent WBV training 3 times a week for 8 weeks.However, no signi cant effect of WBV training on pain was found in comparison with the control group, which performed a similar exercise without the vibration stimulus.Similar to our results, Wang [( 19)], Trans [( 24)] and Bokaeian [(18)] found that the WBV training did not help relieve the pain of KOA patients more effectively.Furthermore, a systematic review and meta-analysis showed that vibration training does not have an additional effective effect on knee pain [(31)].

Physical function
The TUG and 6MWD tests were used to determine the ability to perform daily activities, as commonly reported in related studies [ (17,30)].Compared with other groups, the physical function did not improve more effectively in the WBV group, whereas the TUG and 6MWD results were enhanced after 8 weeks of WBV training and ST.During the physical function test, several factors would the test outcomes, such as the function of balance, mobility, muscle strength, etc.Although the WBV training obviously promoted the increasement of knee muscle, other multiple factors might contribute to undifferentiated results of physical function.Besides, similar to our results, several studies failed to verify the superior effect of WBV on physical function [ (17,22,43)].However, after WBV training with longer or more frequent interventions, the physical function of patients improved signi cantly compared with those that underwent a similar training, as reported by Wang et  This study had several limitations.Firstly, we did not address the factors that might affect the effect of WBV, such as the vibration frequency, displacement and type.Secondly, all the participants were measured at a single centre, and this might have skewed the clinical outcomes.In addition, the participants with mild and moderate KOA were included in this study.Considering the eligibility criteria, the results have limited generalisability and are di cult to apply to patients with severe KOA.In this study, the pain intensity, physical function and neuromuscular function were addressed to determine the e cacy of WBV training.A full exploration of the effects of WBV training on KOA patients was not possible due to the lack of analysis of disease-related biochemical indicators and neuromuscular response.

Conclusion
The current study showed that the advantage of WBV training on muscle strength gain in patients with KOA compared with similar strength training without vibration and health education.Thrice a week for 8 weeks under this protocol didn't result in the alleviation of pain, the improvement of physical function and proprioception.More research is needed in the future to help develop the optimal treatments for KOA.

Supplementary Files
This is a list of supplementary les associated with this preprint.Click to download. CONSORT2010Checklist.doc without vibration.In the study of Park et al. [(23)], the similar effect of WBV in quadriceps muscle strength gain was found compared with the control group.On the contrary, several studies have reported the positive effects of WBV training on neuromuscular function.Trans et al. [(24)] found that two kinds of WBV training regime with different vibration platforms promoted the strength of knee extensors and proprioception in women with KOA separately, which was consistent with the studies of Osugi et al. [(25)], Wang et al. [(26)], and Bokaeian et al. [(18)].These inconsistent results of previous studies hinder the validation of the effects of WBV training on neuromuscular function of patients with KOA.Therefore, the present study aimed to investigate the effect of WBV training on the neuromuscular function of patients with KOA.We conducted a single-blind randomised controlled trial to determine the e cacy of an 8-week WBV training program compared with lower extremity strength training and health education on muscle strength and knee proprioception in individuals with KOA.We hypothesised that WBV training would signi cantly induce muscle strength gain and proprioception improvement of KOA.

Figures
Figures

Figure 1 Changes
Figure 1

Figure 2 Changes
Figure 2

Figure 3 Comparison
Figure 3
3 .Simao AP, Mendonca VA, Avelar NCP, da Fonseca SF, Santos JM, de Oliveira ACC, et al.Whole Body Vibration Training on Muscle Strength and Brain-Derived Neurotrophic Factor Levels in Elderly Woman With Knee Osteoarthritis: A Randomized Clinical Trial Study.Front Physiol.2019;10:756.37. Eklund G, Hagbarth KE.Normal variability of tonic vibration re exes in man.Exp Neurol.
#, Disease severity: mild/ moderate/ severe/very severe/ extrmely severe.All the data were expressed as means ± SD.

Table 3
Amount of changes in proprioception and isokinetic muscle strength by groups.

Table 4
Amount changes in self-reported knee pain and physical function measurements All the data were expressed as means ± SD.HE, health education group; ST, strength training group; WBV, whole body vibration group.