A 1‐year prospective, randomized, double‐blind, and placebo‐controlled trial of 70 postmenopausal women demonstrated that brief periods (<20 minutes) of a low‐level (0.2g, 30 Hz) vibration applied during quiet standing can effectively inhibit bone loss in the spine and femur, with efficacy increasing significantly with greater compliance, particularly in those subjects with lower body mass. Introduction: Indicative of the anabolic potential of mechanical stimuli, animal models have demonstrated that short periods (<30 minutes) of low‐magnitude vibration (<0.3g), applied at a relatively high frequency (20–90 Hz), will increase the number and width of trabeculae, as well as enhance stiffness and strength of cancellous bone. Here, a 1‐year prospective, randomized, double‐blind, and placebo‐controlled clinical trial in 70 women, 3–8 years past the menopause, examined the ability of such high‐frequency, low‐magnitude mechanical signals to inhibit bone loss in the human. Materials and Methods: Each day, one‐half of the subjects were exposed to short‐duration (two 10‐minute treatments/day), low‐magnitude (2.0 m/s² peak to peak), 30‐Hz vertical accelerations (vibration), whereas the other half stood for the same duration on placebo devices. DXA was used to measure BMD at the spine, hip, and distal radius at baseline, and 3, 6, and 12 months. Fifty‐six women completed the 1‐year treatment. Results and Conclusions: The detection threshold of the study design failed to show any changes in bone density using an intention‐to‐treat analysis for either the placebo or treatment group. Regression analysis on the a priori study group demonstrated a significant effect of compliance on efficacy of the intervention, particularly at the lumbar spine (p = 0.004). Posthoc testing was used to assist in identifying various subgroups that may have benefited from this treatment modality. Evaluating those in the highest quartile of compliance (86% compliant), placebo subjects lost 2.13% in the femoral neck over 1 year, whereas treatment was associated with a gain of 0.04%, reflecting a 2.17% relative benefit of treatment (p = 0.06). In the spine, the 1.6% decrease observed over 1 year in the placebo group was reduced to a 0.10% loss in the active group, indicating a 1.5% relative benefit of treatment (p = 0.09). Considering the interdependence of weight, the spine of lighter women (<65 kg), who were in the highest quartile of compliance, exhibited a relative benefit of active treatment of 3.35% greater BMD over 1 year (p = 0.009); for the mean compliance group, a 2.73% relative benefit in BMD was found (p = 0.02). These preliminary results indicate the potential for a noninvasive, mechanically mediated intervention for osteoporosis. This non‐pharmacologic approach represents a physiologically based means of inhibiting the decline in BMD that follows menopause, perhaps most effectively in the spine of lighter women who are in the greatest need of intervention.

Mesenchymal stem cells (MSCs) are defined by their ability to self‐renew and differentiate into the cells that form mesodermal tissues such as bone and fat. Low magnitude mechanical signals (LMMS) have been shown to be anabolic to bone and have been recently reported to suppress the development of fat in normal animals fed a regular diet. Using male C57BL/6J mice, the ability of LMMS (0.2g, 90‐Hz signal applied for 15 min/d, 5 d/wk) to simultaneously promote bone formation and prevent diet‐induced obesity was correlated to mechanical influences on the molecular environment of the bone marrow, as indicated by the population dynamics and lineage commitment of MSCs. Six weeks of LMMS increased the overall marrow‐based stem cell population by 37% and the number of MSCs by 46%. Concomitant with the increase in stem cell number, the differentiation potential of MSCs in the bone marrow was biased toward osteoblastic and against adipogenic differentiation, as reflected by upregulation of the transcription factor Runx2 by 72% and downregulation of PPARγ by 27%. The phenotypic impact of LMMS on MSC lineage determination was evident at 14 wk, where visceral adipose tissue formation was suppressed by 28%, whereas trabecular bone volume fraction in the tibia was increased by 11%. Translating this to the clinic, a 1‐yr trial in young women (15–20 yr; n = 48) with osteopenia showed that LMMS increased trabecular bone in the spine and kept visceral fat at baseline levels, whereas control subjects showed no change in BMD, yet an increase in visceral fat. Mechanical modulation of stem cell proliferation and differentiation indicates a unique therapeutic target to aid in tissue regeneration and repair and may represent the basis of a nonpharmacologic strategy to simultaneously prevent obesity and osteoporosis.