Annals of Biomedical Engineering, Vol. 34, No. 7, July 2006 ( C  2006) pp. 1149–1156 DOI: 10.1007/s10439-006-9133-5 The Effect of Varying Magnitudes of Whole-Body Vibration on Several Skeletal Sites in Mice BLAINE A. CHRISTIANSEN and MATTHEW J. SILVA Departments of Orthopaedic Surgery and Biomedical Engineering, University in St. Louis, 1 Barnes-Jewish Hospital Plaza Campus Box 8233, St. Louis, MO 63110, USA (Received 21 June 2005; accepted 4 May 2006; published online: 20 June 2006) Abstract—It has been reported that whole-body vibration (WBV) is anabolic to trabecular bone in animal models and humans. It is likely that this anabolic response does not occur uniformly throughout the entire body. Two factors that may affect the ob- served anabolic response are vibration magnitude and skeletal site of interest. In this study, mice were loaded with WBV of varying magnitudes. After five weeks of loading, bone mar- row was flushed from tibias in order to quantify osteoprogenitor cells. Staining with alizarin red (an indicator of mineralization) showed a significant decrease in percent stained area in the 0.3 g loaded group compared to the control group and the 1.0 g group. MicroCT analysis was performed at five skeletal sites: the prox- imal tibial metaphysis, femoral condyles, distal femoral metaph- ysis, proximal femur, and L5 vertebral body. Increasing magni- tudes of WBV were associated with a non-dose-dependent in- crease in trabecular bone volume (BV/TV) at the proximal tibial metaphysis, although other sites were unresponsive. There were statistically significant increases in BV/TV in the 0.1 g group (32% increase) and 1.0 g group (43% increase) compared to control (p < 0.05). The 0.1 g and 1.0 g groups also had higher BV/TV than the 0.3 g loaded group. If this non-dose-dependent phenomenon is verified by future studies, it suggests that a range of magnitudes should be examined for each application of WBV. Keywords—Osteoporosis, Trabecular bone, Mechanical loading, Murine, MicroCT, Osteoprogenitor cells, Bone formation. INTRODUCTION Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to fragility and an increased risk of fracture, especially of the hip, spine and wrist. 13 Osteoporosis is one of the most com- mon skeletal pathologies in the United States today, affect- ing an estimated 44 million people. 13 Bone loss is classified as osteoporosis when bone mineral density (BMD) falls 2.5 standard deviations below the mean for a young adult. 12 In recent years it has been shown that high-frequency vi- Address correspondence to Blaine A. Christiansen, Departments of Orthopaedic Surgery and Biomedical Engineering, University in St. Louis,1 Barnes-Jewish Hospital Plaza Campus Box 8233, St. Louis, MO 63110, USA. Electronic mail: bac2@cec.wustl.edu bration can be anabolic to trabecular bone formation both in animal models 1 , 6, 7 , 14, 18–22 and humans, 17 , 25, 29, 30 and thus can potentially increase bone density. Such methods are promising for the treatment of established osteoporosis or for preventing bone loss in aging or bed-ridden patients. Whole-body vibration (WBV) can be applied passively, making it more feasible than a rigorous exercise routine for many patients. In addition, it utilizes the natural response of bone to loading, and therefore would not carry with it the potential side effects that a drug-based treatment could have (weight gain, higher risk of cancer, gastrointestinal problems). 18 The specific mechanisms by which mechanical loading causes bone formation are not fully known, but one of the factors that may influence the degree of bone formation caused by whole-body vibration is vibration magnitude (i.e., peak acceleration). In general, the magnitude of the bone formation response increases with loading magni- tude. 27 Rubin et al. subjected turkeys to WBV at 30 Hz (5 min per day for 30 days) with maximum accelerations of 0.1, 0.2, 0.3, and 0.9 g (where 1.0 g is 9.8 m/s 2 ) . 18 They found that labeled surface (LS) in the trabecular bone of the proximal tibial metaphysis and the trochanteric region of the femur demonstrated a linear dose-dependent increase with increasing vibration magnitude. On the other hand, mineral apposition rate (MAR) was activated by 0.1 g vibration but failed to show further significant increase at higher vibration magnitudes. No investigations of the effect of whole-body vibration magnitude have been reported for mice, although mice have been shown to be responsive to vibrational load- ing. 7 , 24 Mice are of particular interest because they are commonly used for studies of skeletal biology, especially when investigating genetic or molecular factors. Few studies have investigated the effect of whole-body vibration at more than one skeletal site. The sites of great- est interest to orthopaedic research are the proximal femur and the spine, since these are the sites that are most likely to suffer osteoporotic fracture. The most commonly ana- lyzed sites for WBV using animal models are the proximal 1149 0090-6964/06/0700-1149/0 C  2006 Biomedical Engineering Society