Low-Intensity Vibration Protects the Weight-Bearing Skeleton and Suppresses Fracture Incidence in Boys With Duchenne Muscular Dystrophy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Abstract

The ability of low-intensity vibration (LIV) to combat skeletal decline in Duchenne Muscular Dystrophy (DMD) was evaluated in a randomized controlled trial. Twenty DMD boys were enrolled, all ambulant and treated with glucocorticoids (mean age 7.6, height-adjusted Z-scores [HAZ] of hip bone mineral density [BMD] -2.3). Ten DMD boys were assigned to stand for 10 min/d on an active LIV platform (0.4 g at 30 Hz), while 10 stood on a placebo device. Baseline and 14-month bone mineral content (BMC) and BMD of spine, hip, and total body were measured with DXA, and trabecular bone density (TBD) of tibia with quantitative computed tomography (QCT). All children tolerated the LIV intervention well, with daily compliance averaging 78%. At 14 months, TBD in the proximal and distal tibia remained unchanged in placebo subjects (-1.0% and -0.2%), while rising 3.5% and 4.6% in LIV subjects. HAZ for hip BMD and BMC in the placebo group declined 22% and 13%, respectively, contrasting with no change from baseline (0.9% and 1.4%) in the LIV group. Fat mass in the leg increased 32% in the placebo group, contrasting with 21% in LIV subjects. Across the 14-month study, there were four incident fractures in three placebo patients (30%), with no new fractures identified in LIV subjects. Despite these encouraging results, a major limitation of the study is-despite randomized enrollment-that there was a significant difference in age between the two cohorts, with the LIV group being 2.8y older, and thus at greater severity of disease. In sum, these data suggest that noninvasive LIV can help protect the skeleton of DMD children against the disease progression, the consequences of diminished load bearing, and the complications of chronic steroid use. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Keywords: BIOMECHANICS; BONE MINERAL CONTENT; BONE MINERAL DENSITY; EXERCISE; OSTEOPOROSIS.

Fig. 1

CONSORT diagram for the Duchenne low intensity vibration trial. CONSORT = Consolidated Standards of Reporting Trials.

Fig. 2

QCT measured changes (mean ± SD) at 14 months in TBD in distal tibia. TBD did not change in placebo (circles, 0.2% below baseline, p = 0.43), in some contrast with TBD increases typical to healthy boys of the same age.^{( 73 )} LIV increased TBD by 4.6% (squares, p < 0.20 from baseline). Unfortunately, because of the loss of subject‐specific compliance records, the ability to correlate non‐responders (eg, two LIV subjects that lost TBD) to their daily use of the device was not possible.

Fig. 3

Absolute change in TBLH (left) and hip (right) BMD HAZ score from baseline (mean ± SD). The 14‐month decrease from baseline in TBLH was significant for both placebo and LIV groups (p < 0.05), but the differences between groups was not different (p = 0.95). In contrast, the absolute decrease in HAZ hip BMD was significant in the placebo group (p < 0.05), but there was no change from baseline in LIV.

Fig. 4

Percent increase (mean ± SD) from baseline in fat mass for TBLH (left) and hip (right). The 14‐month increase from baseline in TBLH was significant (p < 0.05) for both placebo (circles) and LIV (squares) groups, but the differences between groups was not different (p = 0.95). DXA measured fat mass of left leg showed increases in both placebo (circles; 32.1%) and LIV (squares; 21.6%) DMD subjects. Subject‐specific changes showed a 40% suppression of fat mass in LIV as compared to placebo groups (p < 0.20).

Fig. 5

DXA measured percent change (mean ± SD) in BMC at hip and spine at 14 months within placebo (circles) and LIV (squares) subjects, as normalized to changes in arm (intrasubject control). Hip BMC in placebo decreased by 5.2%, while the LIV group increased by 4.0%, a 9.2% shift (p < 0.20). BMC in spine dropped 5.9% in placebo, and increased 4.4% in LIV, a 10.2% shift (p < 0.05).

Fig. 6

DXA measured percent change (mean ± SD) at 14 months in BMD in placebo (circles) and LIV subjects (squares), as normalized to changes in arm (intrasubject control). Hip BMD in the placebo decreased by 3.8%, while LIV remained unchanged (0.02%), a 3.5% shift (p < 0.20). BMD spine increased 1.7% in placebo, and 4.7% in LIV, a 3.0% shift (p < 0.20).

Fig. 7

Absolute number of incident fractures (left) and subjects with fracture (right) identified across the 14‐month protocol in both placebo and LIV group (N = 10 subjects in each group). Although the causes of the fractures are not known, the difference between groups is significant (p < 0.05).

Fig. 8

Mean difference (%) in 14‐month changes between LIV and placebo subjects. The error bars represent the standard error of the difference, calculated as the square root of the sum of squared SDs of the 14‐month changes in LIV and control subjects. Although fat mass in the leg of LIV subjects decreases relative to placebo subjects, parameters directly related to bone quantity/quality increase. The small differences in changes at the arm between LIV and placebo subjects are intended to represent an internal control, emphasizing that this region changes very little across 14 months.