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Calcified Tissue Internationaland Musculoskeletal Research ISSN 0171-967XVolume 95Number 6 Calcif Tissue Int (2014) 95:547-556DOI 10.1007/s00223-014-9920-1

Effect of Whole-Body Vibration onCalcaneal Quantitative UltrasoundMeasurements in Postmenopausal Women:A Randomized Controlled Trial

Lubomira Slatkovska, Joseph Beyene,Shabbir M. H. Alibhai, Queenie Wong,Qazi Z. Sohail & Angela M. Cheung

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ORIGINAL RESEARCH

Effect of Whole-Body Vibration on Calcaneal QuantitativeUltrasound Measurements in Postmenopausal Women:A Randomized Controlled Trial

Lubomira Slatkovska • Joseph Beyene •

Shabbir M. H. Alibhai • Queenie Wong •

Qazi Z. Sohail • Angela M. Cheung

Received: 3 July 2014 / Accepted: 14 October 2014 / Published online: 12 November 2014

� Springer Science+Business Media New York 2014

Abstract The purpose of this study was to examine the

effect of whole-body vibration (WBV) on calcaneal

quantitative ultrasound (QUS) measurements; which has

rarely been examined. We conducted a single-centre,

12-month, randomized controlled trial. 202 postmeno-

pausal women with BMD T score between -1.0 and -2.5,

not receiving bone medications, were asked to stand on a

0.3 g WBV platform oscillating at either 90- or 30-Hz for

20 consecutive minutes daily, or to serve as controls.

Calcium and vitamin D was provided to all participants.

Calcaneal broadband attenuation (BUA), speed of sound,

and QUS index were obtained as pre-specified secondary

endpoints at baseline and 12 months by using a Hologic

Sahara Clinical Bone Sonometer. 12-months of WBV did

not improve QUS parameters in any of our analyses. While

most of our analyses showed no statistical differences

between the WBV groups and the control group, mean

calcaneal BUA decreased in the 90-Hz (-0.4 [95 % CI

-1.9 to 1.2] dB MHz-1) and 30-Hz (-0.7 [95 % CI -2.3

to 0.8] dB MHz-1) WBV groups and increased in the

control group (1.3 [95 % CI 0.0–2.6] dB MHz-1).

Decreases in BUA in the 90-, 30-Hz or combined WBV

groups were statistically different from the control group in

a few of the analyses including all randomized participants,

as well as in analyses excluding participants who had

missing QUS measurement and those who initiated hor-

mone therapy or were \80 % adherent. Although there are

consistent trends, not all analyses reached statistical sig-

nificance. 0.3 g WBV at 90 or 30 Hz prescribed for 20 min

daily for 12 months did not improve any QUS parameters,

but instead resulted in a statistically significant, yet small,

decrease in calcaneal BUA in postmenopausal women in

several analyses. These unexpected findings require further

investigation.

L. Slatkovska � S. M. H. Alibhai � Q. Wong �A. M. Cheung (&)

Osteoporosis Program, University Health Network/Mount Sinai

Hospital, 200 Elizabeth Street, 7 Eaton North, Room 221,

Toronto, ON, Canada

e-mail: angela.cheung@uhn.ca

L. Slatkovska � Q. Wong � Q. Z. Sohail � A. M. Cheung

Women’s Health Program, University Health Network, Toronto,

ON, Canada

L. Slatkovska � S. M. H. Alibhai � A. M. Cheung

Institute of Medical Science, University of Toronto, Toronto,

ON, Canada

J. Beyene � A. M. Cheung

Dalla Lana School of Public Health, University of Toronto,

Toronto, ON, Canada

J. Beyene

Department of Clinical Epidemiology & Biostatistics, McMaster

University, Hamilton, ON, Canada

S. M. H. Alibhai � Q. Z. Sohail � A. M. Cheung

Department of Medicine, University of Toronto, Toronto, ON,

Canada

S. M. H. Alibhai � A. M. Cheung

Institute of Health Policy, Management and Evaluation,

University of Toronto, Toronto, ON, Canada

Q. Wong � A. M. Cheung

Centre of Excellence in Skeletal Health Assessment, Joint

Department of Medical Imaging, University of Toronto,

Toronto, ON, Canada

123

Calcif Tissue Int (2014) 95:547–556

DOI 10.1007/s00223-014-9920-1

Author's personal copy

Keywords Whole-body vibration � Menopause �Quantitative ultrasound � Calcaneus � Randomized

controlled trial

Introduction

Whole-body vibration (WBV) therapy involves the trans-

mittance of mechanical vibrations to the musculoskeletal

system by means of an oscillating platform. Various types

of WBV platforms exist on the market and have been

investigated in clinical trials. These platforms vary in terms

of vibration frequencies (Hz) and vertical accelerations

(g) [1]. Duration of the WBV protocol, treatment frequency

(number of treatments per day and rest periods between

treatments), and treatment duration have also varied in

previous investigations [1]. Therefore, currently it is

unclear which WBV regimen produces the most desired

effect of WBV on the skeleton with minimal deleterious

effects on the rest of the body [1].

The calcaneus is the closest skeletal site to the WBV

platform. When standing on a platform with vertical

accelerations, the vibrations are transmitted through the

feet to the weight-bearing skeleton, and typically become

weaker as the distance from the platform increases, because

of the cushioning (or dampening) provided by major joints

and soft-tissue [2, 3]. The calcaneus, however, is separated

from the source of vibration by only a thin layer of soft

tissue, and thus is directly in contact with the platform

accelerating upwards. It is almost entirely composed of

trabecular bone, which is more metabolically active and

may respond faster to treatment than cortical bone.

Changes in the calcaneal bone are commonly measured

using quantitative ultrasound (QUS), which projects ultra-

sound waves through the heel, and thereby collects dif-

ferent information about bone material properties than

bone densitometry tools such as dual-energy X-ray

absorptiometry (DXA) and high-resolution peripheral

quantitative computed tomography (HR-pQCT). QUS

parameters, broadband attenuation (BUA) and speed of

sound (SOS), provide relatively good estimates of calca-

neal BMD, and BUA in particular may also reflect tra-

becular microarchitectural properties [4, 5]. Yet the effect

of WBV therapy on the calcaneus has rarely been exam-

ined using QUS [1, 6, 7].

Randomized controlled trials (RCTs) of WBV therapy

in postmenopausal women have primarily examined hip

and lumbar spine areal BMD obtained with DXA [6–12]. A

statistically significant, although clinically small, increase

was seen at the hip in two trials [8, 10], but none of the

trials found a significant effect at the lumbar spine. Volu-

metric BMD at the distal tibia obtained with HR-pQCT

showed no significant changes in postmenopausal women

in two trials [12, 13]. To our knowledge, calcaneal

assessment using QUS was performed in only one RCT of

WBV in postmenopausal women [7]. A significant

improvement in calcaneal BUA was found in response to

twice-weekly, 6-minute sessions of WBV at C1 g and

12.5 Hz (3.4 %, p = 0.05), but not in response to twice-

weekly, 15-minute sessions of WBV at 0.3 g and 30 Hz

(-0.8 %, p = 0.44) or no WBV (-3.1 %, p = 0.08) [7].

However, no significant between-group differences in BUA

changes were found and SOS was not reported [7]. Fur-

thermore, the trial was small (n = 47) with short follow-up

duration (8 months), and vitamin D adequacy was not

documented [7].

We conducted a 12-month RCT in 202 postmenopausal

women who were provided with calcium and vitamin D

supplements, and compared effects of daily 20-minute

WBV at 0.3 g and 90- or 30-Hz with no WBV (Vibration

Study). We have previously reported on our main outcomes

[12]; no effect of WBV was found on distal tibial volu-

metric BMD and parameters of bone microstructure

assessed by HRpQCT, or hip and spine areal BMD asses-

sed by DXA [12]. Calcaneal QUS outcomes were collected

as pre-specified secondary endpoints and examined sepa-

rately, as we expected the calcaneus to receive a more

intense WBV stimulus due to its proximity to the oscil-

lating platform than our primary endpoint location (distal

tibia). Our a priori hypothesis was that year-long, daily

20-min WBV therapy will improve calcaneal QUS out-

comes. In this paper, we are reporting the results of the

QUS outcomes of the vibration study.

Methods

Trial Design, Setting, and Randomization

A 12-month, superiority RCT with three parallel arms was

conducted at the Postmenopausal Health Research Clinic

of Toronto General Hospital, University Health Network,

Toronto, Canada. Recruitment started in October 2006 and

finished in November 2008 when the target sample size

was achieved. Calcaneal QUS measurements were

obtained as pre-specified secondary endpoints at baseline

and 12 months. HR-pQCT and DXA outcomes were col-

lected and reported previously [12].

A computer-generated block-randomization scheme

with 1:1:1 allocation ratio and block size of 12 was used

to assign eligible participants to receive one of three

interventions: WBV at 0.3 g and 90 Hz, WBV at 0.3 g

and 30 Hz, or no WBV (control group). Sealed envelopes

containing participant number and group allocation were

opened sequentially at baseline after eligibility criteria

were satisfied and baseline calcaneal QUS outcomes were

548 L. Slatkovska et al.: Effect of WBV on Calcaneal QUS Measurements

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collected. Sham WBV was not utilized in controls and

QUS outcome assessment was not blinded. Participants

knew whether or not they were controls, but were una-

ware of the 90-Hz versus 30-Hz group assignment. The

trial was approved by the University Health Network

research ethics board, registered at the ClinicalTrials.gov

(#NCT00420940) and funded by the Physicians’ Services

Incorporated Foundation.

Participants

Potential participants were recruited in the Greater Toronto

Area primarily by using posted flyers, word of mouth and

our postmenopausal health newsletter. Women were eli-

gible if they had experienced cessation of menses 1 or more

years prior and their lowest BMD T score at the lumbar

spine, femoral neck, or total hip was between -1.0 and

-2.5. We excluded women with a BMD T score greater than

-1.0, because previous research has shown that less-dense

bones may have a greater response to WBV [11, 14, 15].

Other exclusion criteria included osteoporosis (BMD

T score of B-2.5); fragility fracture after age 40; sec-

ondary causes of bone loss; other metabolic bone diseases

or diseases affecting bone metabolism; history of active

cancer in the past 5 years; body mass of C90 kg; knee or

hip joint replacements; spinal implants; use of hormone

therapy in the past 12 months, raloxifene or teriparatide in

the past 6 months, or bisphosphonates for C3 months or

within the past 3 months; chronic glucocorticoid, antico-

agulant or anticonvulsant therapy; inability to tolerate

WBV for 20 consecutive minutes at screening; and

expected changes in physical activity levels or out-of-town

travels for more than four consecutive weeks.

Interventions and Adherence

Participants randomized to the 90- or 30-Hz groups were

given WBV platforms synchronously oscillating at a fre-

quency of 90- or 30-Hz, respectively, with a peak acceler-

ation or magnitude of 0.3 g (peak-to-peak displacement

of \50 lm), provided by Juvent Regenerative Technologies

Corporation, Riveria Beach, Florida [16]. At baseline, the

participants were instructed to stand erect on the oscillating

platform at home for 20 consecutive minutes daily for

12 months, with neutral posture at the neck, lumbar spine,

and knees, wearing socks or barefoot, and without excessive

foot or body movements. Self-reported adherence to WBV

was obtained at 6 months and feedback was provided.

Actual adherence was extracted from each WBV platform at

12 months by using an internal clock that recorded the date,

time, and duration of every session. Percentage of adherence

to WBV was calculated on the basis of total cumulative

duration of WBV performed during the study [(total minutes

of WBV performed at any time during study participa-

tion) 7 (total study days 9 20 min) 9 100].

We chose to examine a magnitude of 0.3 g, because

lower WBV magnitudes (0.3 vs. 0.6 g) were previously

found to be more effective on bone in adult female mice

[17]. Further, we compared 90- and 30-Hz frequencies,

since at 0.2 g, WBV at 90-Hz was shown to be more

effective than WBV at 45-Hz in ovariectomized rats [18],

and no RCTs up to date have compared high versus low

frequencies. Finally, we chose a dose of 20 consecutive

minutes a day, because WBV at 0.3 g and 30-Hz was found

to have no significant effect on hip or spine areal BMD in

postmenopausal women treated for 10 min twice daily for

12-months, while a significant increase in trabecular BMD

was found at the femur in adult ewes treated for 20 con-

secutive minutes 5 days a week for 12 months [11, 19].

Our WBV protocol was considered safe based on the

International Organization for Standardization recommen-

dations in industries that use machinery involving vibration

(ISO 2631) [2, 11, 20].

Control participants were asked not to use WBV thera-

pies. Calcium and vitamin D supplements were provided to

all participants at baseline and 6 months, so that their total

daily intakes from diet plus supplements approximated

1,200 mg and 1,000 IU, respectively, as estimated by a

validated recall questionnaire [21]. Calcium and vitamin D

intakes were additionally assessed at 12 months using the

same validated recall questionnaire [21], at which point

self-reported estimates of overall adherence to calcium and

vitamin D supplements were also obtained.

Outcomes and Follow-Up

Calcaneal QUS measurements were collected as second-

ary endpoints, because beneficial effects of WBV on bone

were found to be more pronounced within the trabecular

versus cortical bone tissue, and at weight-bearing skeletal

sites located closer to the oscillating platforms in previous

studies [22, 23]. BUA (dB MHz-1), SOS (m s-1), and

QUS index (QUI, 0.41 9 [BUA ? SOS] - 571) were

obtained at baseline and at 12 months using a Sahara

Clinical Bone Sonometer (Hologic, Bedford, MA). QUS

assesses the speed (i.e., SOS) and attenuation (i.e., BUA)

of an ultrasound beam as it passes through the calcaneus,

and QUI combines these two results linearly and re-scales

them into heel BMD units. Therefore, both BUA and SOS

reflect calcaneal BMD status: the denser the calcaneal

bone, the greater the attenuation and speed of the ultra-

sound wave [4, 5, 24]. However, BUA has been found to

also reflect trabecular microarchitecture status, possibly

because as the ultrasound waves pass through bone they

may become scattered and absorbed by the trabecular

scaffolding [4, 5, 24].

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A single, trained assessor performed calibration and

measurements in the same room and using the same

device for the entire duration of data collection. Cali-

bration was performed on the day of measurement using a

manufacturer-specific phantom, and if unacceptable

quality control values were obtained, calibration was

repeated until satisfactory. The quality control values for

BUA and SOS were stable throughout our study period,

with the exception of a slight upward drift in BUA in the

last 2 months. During each measurement, all participants

were asked to sit still in the same chair with the non-

dominant foot placed in a marked area on the device

according to manufacturer instructions to minimize mea-

surement error. If a measurement was indicated as invalid

by the device, it was repeated up to three times. Two

sources of error were identified and resulted in the

exclusion of several QUS measurements from the ana-

lysis: (1) unsuccessful calibration on the day of mea-

surement and (2) invalid measurement after three attempts

as indicated by the device, often due to ankle edema. The

root mean square coefficients of variation for short-term

reproducibility of calcaneal BUA, SOS, and QUI mea-

surements in our laboratory were 2.8, 0.2, 2.5 % and the

corresponding least significant changes were 7.6, 0.7,

6.9 %, respectively, which is in agreement with other

laboratories using the same QUS model [24].

Data on medical conditions, medications, and falls were

collected at each study visit, and participants were also asked

to inform us by telephone of any health changes they expe-

rienced during the study. Adverse events (defined as any

untoward effects with an onset after baseline or worsening of

an existing condition) were recorded by using the Common

Terminology Criteria for Adverse Events version 3 from the

US National Cancer Institute [25]. Total physical activity

levels were estimated at baseline and 12-months from the

daily activity metabolic index (AMI; kcal day-1) by using

the Minnesota Leisure-Time Physical Activity Question-

naire [26]. Total physical activity levels were further divided

into light, moderate, and heavy physical activity levels based

on each activity’s metabolic index (light AMI =

B4 kcal day-1; moderate AMI = 4.5–5.5 kcal day-1;

heavy AMI = C6 kcal day-1).

Statistical Analyses

Between-group differences in absolute change from

baseline (12 months—baseline) in calcaneal QUS out-

comes were assessed by using one-way analysis of var-

iance and a priori specified contrasts (90-Hz WBV vs.

control, 30-Hz WBV vs. control, 90-Hz WBV vs. 30-Hz

WBV, and combined 90- and 30-Hz WBV vs. control).

Various multiple imputation models were used for

missing QUS outcomes in the intent-to-treat approach

[27]. Participants with missing QUS outcomes (due to

loss of follow-up or invalid, uncalibrated, or unattained

QUS measurement) or those who initiated hormone

therapy during the study were excluded from the per

protocol approach. Finally, we also excluded participants

with \80 % adherence to WBV from the per protocol

data, as we hypothesized a priori to observe a greater

effect of WBV in more adherent participants. The

adherence threshold of 80 % was chosen a priori. Self-

reported adherence to calcium and vitamin D supple-

ments and 12-month changes in calcium and vitamin D

intakes and physical activity levels were compared

between groups using one-way analysis of variance.

Sample size calculations for this RCT were based on our

pre-specified primary outcome, tibial trabecular volu-

metric BMD, as outlined in our primary report [12]. All

analyses were performed using SAS, version 9.3 (SAS

Institute, Cary, NC) with a P \ 0.05 indicating statistical

significance.

Results

Participants

Of the 1,126 subjects initially screened for eligibility, 202

postmenopausal women met our eligibility criteria and

were randomly assigned to the 90-Hz WBV (67 partici-

pants), 30-Hz WBV (68 participants), or control (67 par-

ticipants) groups (Fig. 1). Eligible participants were the

same postmenopausal women as those examined in our

primary report [12]. Relevant baseline characteristics did

not significantly differ between groups and are summarized

in Table 1.

At the end of the trial, QUS outcomes were missing in

25 participants due to drop-out (n = 7), unattained final

measurement (n = 4), invalid measurement (n = 7), and

unsuccessful calibration (n = 7). Two participants (1 each

in the 90-Hz WBV and control groups) started hormone

therapy, but returned for the final assessment. In addition,

adherence to WBV was not obtained in three participants

because their platform’s digital clock malfunctioned, and

in five of the participants who dropped out. Most partici-

pants were either close to 100 or 0 % adherent and the

median adherence based on the total cumulative duration of

WBV was 79 % (interquartile range 41–91 %) for the

90-Hz WBV group and 77 % (interquartile range

55–86 %) for the 30-Hz WBV group. Furthermore, self-

reported adherence to calcium and vitamin D supplements,

12-month changes in total daily calcium or vitamin D

intakes, and 12-month changes in light, moderate, heavy,

and total physical activity levels were similar between the

three groups (data not shown).

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Fig. 1 Participants’ progress through trial. WBV whole-body vibration, QUS quantitative ultrasound

Table 1 Baseline characteristics of the study population

Baseline characteristics 90-Hz WBV group (n = 67) 30-Hz WBV group (n = 68) Control group (n = 67)

Age (years), mean (SD) 60.5 (7.0) 59.6 (6.0) 60.8 (5.5)

Years since menopause, mean (SD) 10.2 (8.3) 10.8 (7.3) 10.5 (7.5)

Ethnicity, n (%)

European 55 (82) 48 (70) 54 (81)

Southeast Asian 8 (12) 14 (20) 10 (15)

Other 4 (6) 6 (9) 3 (4)

Mass (kg), mean (SD) 64.4 (10.6) 62.0 (10.5) 62.4 (9.5)

Body mass index (kg m-2), mean (SD) 24.9 (4.0) 24.5 (3.6) 24.2 (3.4)

Height (m), mean (SD) 1.61 (0.06) 1.59 (0.06) 1.60 (0.06)

Total daily calcium intake (mg), mean (SD)a 1,538 (677) 1,399 (656) 1,352 (642)

Total daily vitamin D intake (IU), mean (SD)a 866 (582) 778 (583) 808 (584)

Calcaneal quantitative ultrasound measurements, mean (SD)

BUA (dB MHz-1) 72.2 (13.0) 75.4 (14.7) 72.0 (12.9)

SOS (m s-1) 1,538.0 (28.3) 1,542.7 (23.9) 1,538.6 (23.5)

QUI 89.2 (16.3) 92.4 (14.8) 89.3 (14.4)

BUA broadband attenuation, QUI quantitative ultrasound index, SD standard deviation, SOS speed of sound, WBV whole-body vibrationa Total daily intake from diet plus patient’s own supplements, prior to providing study supplements

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Calcaneal Quantitative Ultrasound Outcomes

After 12 months, we found no improvement in BUA, SOS,

or QUI in any of the WBV groups when compared to con-

trols. Instead, in our intent-to-treat analyses (n = 202), we

found statistically significant decreases in BUA in the 30-Hz

WBV group when compared to the control group in 2 out of

4 multiple imputation models analyses (Table 2). We also

found a trend in decrease in BUA in the 90-Hz WBV group

compared to controls although not statistically significant. In

the per protocol approach (n = 175), upon exclusion of

participants with missing QUS measurement (n = 25) and

those who initiated hormone therapy during the study

(n = 2), statistically significant decreases in BUA were seen

in the 30-Hz versus the control group and the 30- and 90-Hz

WBV combined groups compared to the control group, but

not in the 90-Hz versus the control group (Table 3). When

we additionally excluded participants with \80 % adher-

ence to WBV, a significant decrease in BUA was seen in the

90-Hz group versus the control group, but not in the 30-Hz

versus the control group (Table 3). Using the per protocol

data, the magnitude of WBV treatment effect, defined as the

difference in mean BUA change between control group

(1.3 dB MHz-1 or 2.0 %) and 90-Hz (–0.4 dB MHz-1 or

-0.2 %) or 30-Hz (-0.7 dB MHz-1 or -0.6 %) WBV

groups, was -1.7 dB MHz-1 or -2.2 % for 90-Hz partic-

ipants and -2.1 dB MHz-1 or -2.6 % for 30-Hz partici-

pants. Throughout all our analyses, the decrease in BUA did

not significantly differ between 90- and 30-Hz WBV groups.

Although, SOS and QUI showed a decreasing trend in the

30- and 90-Hz WBV groups as compared to the control

group in all analyses, none were statistically significant

(Tables 2 and 3).

Adverse Events

Several women in the 90- and 30-Hz WBV groups spon-

taneously reported minor foot-related problems that they

attributed to WBV therapy. Some complained of plantar

foot pain (two in 90-Hz and one in 30-Hz WBV group)

lasting throughout the day, while others reported foot

numbness (two in each 90- and 30-Hz WBV groups) or toe

cramping (two in 90-Hz WBV group) that lasted briefly

during or just after a WBV session. As summarized in our

primary outcome report, no serious adverse events were

caused by WBV, and quantitative analyses of various

Table 2 Intent-to-treat analysis: between-group differences in absolute change from baseline in calcaneal quantitative ultrasound outcomes in

the multiple imputation models

Modela Variables included in the model Calcaneal

quantitative

ultrasound

outcome

Between-group difference

in absolute change from

baseline

P value for pair-wise

comparison

90-Hz

WBV

group–

control

group

30-Hz

WBV

group–

control

group

90-Hz WBV

group versus

control group

30-Hz WBV

group versus

control group

1 Baseline and 12-month change in calcaneal BUA,

SOS, and QUI plus baseline variablesbBUA (dB MHz-1) -1.5 -1.8 0.144 0.102

SOS (m s-1) -1.6 -0.9 0.379 0.620

QUI -1.3 -1.1 0.220 0.305

2 Baseline and 12-month change in calcaneal BUA,

SOS, and QUI plus 12-month change in DXA

and HR-pQCT outcomesc plus baseline

variablesb

BUA (dB MHz-1) -1.8 -2.1 0.112 0.037

SOS (m s-1) -1.2 -0.9 0.497 0.585

QUI -1.2 -1.2 0.226 0.198

3 12-month change in calcaneal BUA, SOS and

QUI, and in DXA and HR-pQCT outcomescBUA (dB MHz-1) -1.8 -2.3 0.087 0.026

SOS (m s-1) -1.4 -1.8 0.444 0.361

QUI -1.3 -1.6 0.210 0.123

4 Baseline and 12-month change in calcaneal BUA,

SOS, and QUI

BUA (dB MHz-1) -1.4 -1.8 0.245 0.080

SOS (m s-1) -1.0 -1.0 0.552 0.569

QUI -1.0 -1.1 0.326 0.252

BUA broadband attenuation, DXA dual-energy X-ray absorptiometry, HR-pQCT high-resolution peripheral quantitative computed tomography,

QUI quantitative ultrasound index, SOS speed of sound, WBV whole-body vibrationa Four multiple imputation models were used for missing QUS outcomes in 25 participants, by using different sets of variables in each modelb Baseline variables included age, mass, height, body mass index, age at menarche and years since menopausec DXA outcomes included BMD at the femoral neck, total hip and lumbar spine, and HR-pQCT outcomes included trabecular BMD thickness,

number and separation at the distal tibia; all were examined in our primary outcome report

552 L. Slatkovska et al.: Effect of WBV on Calcaneal QUS Measurements

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L. Slatkovska et al.: Effect of WBV on Calcaneal QUS Measurements 553

123

Author's personal copy

adverse events, including those involving the lower

extremities, revealed no significant between-group differ-

ences [12].

Discussion

In our 12-month RCT of 202 postmenopausal women,

WBV at 90- and 30-Hz did not improve BUA, SOS, or

QUI. Instead, a statistically significant decrease in calca-

neal BUA was found in participants who received 90- or

30-Hz WBV therapy at 0.3 g, compared to no WBV

therapy in some, albeit not all of our analyses. This nega-

tive effect of WBV observed in our trial was unexpected

and its clinical relevance is uncertain, for the decrease

is small (90-Hz: -1.7 dB MHz-1 or -2.2 %; 30-Hz:

-2.1 dB MHz-1 or -2.6 %). To put this into perspective

for the Hologic Sahara device, the least significant change

typically obtained for calcaneal BUA is 7.5–13.9 % for an

individual [24], and the absolute difference in mean cal-

caneal BUA observed between postmenopausal women

with and without osteoporotic fracture is -19.3 db MHz-1

[28].

We had expected an increase in calcaneal BUA, as the

beneficial effects of WBV on bones, particularly those

involving the trabecular tissue at weight-bearing sites

located close to the oscillating platform, were previously

reported in children and animal models [17–19, 29, 30].

Furthermore, in an RCT of postmenopausal women, a

smaller decrease in calcaneal BUA was observed in

response to twice-weekly 15-min sessions of WBV at

0.3 g and 30-Hz (-0.8 %) compared to no WBV

(-3.1 %), and an improvement in calcaneal BUA was seen

in response to twice-weekly 6-minute sessions of WBV

at C1 g and 12.5 Hz (?3.4 %); however, these between-

group differences were not statistically significant [7].

Though our results differ from this previous RCT, the

discrepancy may be because we examined more partici-

pants (n = 202 vs. n = 47) and asked the participants to

stand on the WBV platform more frequently (daily versus

twice a week) over a longer period of follow-up (12 vs.

8 months) [7, 12]. We also examined calcaneal SOS and

QUI, and thus offer additional information about potential

WBV effect on the calcaneus [7, 12]. QUI is a mathe-

matical sum of BUA and SOS and may provide more

clinical insight due to its composite nature [24]. While

bone acoustic properties are primarily influenced by the

mineralized bone matrix and both SOS and BUA corre-

spond to BMD changes, BUA is also thought to be espe-

cially influenced by the trabecular microarchitecture [4, 5,

31–33]. This is possibly because as sound waves pass

through the bone they may become scattered and attenu-

ated by the trabecular structure. Therefore, when a small

but significant effect is found in BUA alone, and not in

SOS and QUI, it may be interpreted as trabecular archi-

tecture being affected in the absence of bone density

changes. Finally, compared to the other trial, we observed

increases in QUS parameters in the control group and not

decreases as would be expected in a prospective follow-up

of postmenopausal women [7, 12]. This increase was

possibly due to vitamin D supplementation in our study

[24]. However, similar increases would be expected in the

WBV groups, since all participant were provided with

vitamin D supplements as part of the trial.

Several limitations existed in our trial. First, sample size

and power calculations were not based on calcaneal QUS

outcomes, because they were collected as secondary end-

points. In addition, women and the outcome assessor were

not blinded to control intervention, since sham WBV was

not provided due to limited funding and a lack of effective

masking of true WBV by a sham platform [11]. Also, since

the control group participants were not instructed to stand

still for 20 consecutive minutes every day, it is unclear

whether just standing on the vibration platform, regardless

of WBV, could have contributed to the between-group

differences in 12-month changes in BUA. Further, QUS

outcomes were missing in 12 % of the participants and

required replacements by the use of multiple imputation

models in our primary analysis. Finally, numerous

between-group comparisons were performed during vari-

ous statistical approaches, thus increasing the likelihood of

chance findings. However, our finding of a decrease in

BUA with WBV was consistent across several analyses and

the number of missing outcomes was similar between

groups.

In spite of these limitations, our results challenge the

existing safety data of WBV in postmenopausal population

if used long-term, and call for future research to consider

this potential adverse effect and confirm our preliminary

findings. If this negative effect is real, several mechanisms

may explain it. First, the small decrease in calcaneal BUA

in women receiving 90- or 30-Hz WBV may be due to

minor bone damage caused by 20 consecutive minutes of

daily WBV for 12 months, with an insufficient rest period

between treatments [34, 35]. When women were standing

on the WBV platform, their heel bones were hit by a small

force (*18 N) of the platform accelerating upwards,

30–90 times per second consecutively for 20 min (i.e.,

36,000–108,000 compressions), where only a thin layer of

soft tissue but no major joints provided cushioning. Since

the calcaneus is made up of mostly trabecular tissue and

BUA decreased more than SOS in the 90- and 30-Hz WBV

groups, there may be minute damage to the trabecular

structure, similar to stress fractures which can occur with

minimal but frequently repeated ground reaction forces

such as walking. Second, perhaps the regulatory

554 L. Slatkovska et al.: Effect of WBV on Calcaneal QUS Measurements

123

Author's personal copy

mechanisms involving either bone fluid flow or skeletal

muscle activation, which may be responsible for increasing

bone formation in response to WBV, were insufficient to

compensate for small structural damage occurring at the

calcaneus [36, 37]. This may be especially true in post-

menopausal women, since they experience slower bone

formation than resorption due to menopause, as compared

to, for example, children and adolescents whose bone

formation surpasses resorption [38].

Finally, since QUS measurements can be affected by

changes in the heel soft tissue [24, 39], such as thickness or

composition, these variables should also be collected in

future research of WBV. It is plausible that at least part of

the decrease in calcaneal BUA observed in our trial may

have occurred due to heel soft tissue damage caused by

WBV, rather than bone damage [24, 40, 41]. Several foot-

related problems, such as pain and numbness, were spon-

taneously reported by the 90- and 30-Hz participants and

attributed to WBV. In occupational settings, where drilling

(with much higher magnitudes of vibration) is involved,

prolonged exposures to vibration of the hands and feet

were also found to cause injuries to the muscles, vascula-

ture, and connective tissues [42, 43].

In conclusion, we found no beneficial effect of WBV on

calcaneal QUS measurements in community-dwelling

postmenopausal women receiving 0.3 WBV at 90 or

30 Hz, but instead a small but statistically significant

decrease in calcaneal BUA in two out of four multiple

imputation models, per protocol analysis and subgroup

analysis of 80 % adherent participants. This potential

negative effect needs to be confirmed in future research. In

the absence of any clear beneficial bone effects at hip,

spine, distal tibia, and calcaneus, we do not recommend

WBV therapy at this time for the prevention of bone loss in

postmenopausal women with low bone density.

Acknowledgments The authors thank the women who volunteered

their time and participated in this trial. We also thank OsTek

Orthopaedics Inc. for their assistance in obtaining the platforms. In

addition, we thank Alice Demaras, Diana Yau, Claudia Chan, Gail

Jefferson, and Farrah Ahmed and our research volunteers and work-

study students who helped with various aspects of the study.

Conflicts of Interest Please note that Lubomira Slatkovska, Joseph

Beyene, Shabbir M. H. Alibhai, Queenie Wong, Qazi Z. Sohail, and

Angela M. Cheung declare that they have no conflicts of interest. All

authors made substantial contributions to the intellectual content of

the paper. A peer-reviewed grant from the Physicians’ Services

Incorporated Foundation funded this trial. Juvent Inc. supplied the

WBV platforms and Jamieson Laboratories provided calcium and

vitamin D supplements. None of these sources were involved in the

study design, conduct, analysis, interpretation of the data, preparation

of this manuscript, or decision to submit the manuscript for

publication.

Human and Animal Rights and Informed Consent All proce-

dures performed in studies involving human participants were in

accordance with the ethical standards of the institutional and/or

national research committee and with the 1964 Helsinki declaration

and its later amendments or comparable ethical standards. Informed

consent was obtained from all individual participants included in the

study.

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