In addition, people with osteoporosis are at high risk of fracture and the best method of fracture prevention in this group is to maintain bone mass. These clinical problems have led to the investigation of methods of mechanical stimulation to improve bone mass and healing, including LMHFV, applied by having the subject stand on a vibrating platform[ 39 - 41 ].
The acceleration used during these experiments is usually very low less than the acceleration due to gravity and the magnitude is typically less than 1 mm. The frequency varies between studies, commonly ranging from 10 to Hz. In addition to different inputs, a variety of different outcomes have been measured. These include bone mineral density BMD , trabecular width or trabecular spacing and bone formation rate BFR , but also include measures of balance[ 42 ], likelihood of falls[ 43 ] and jump height[ 44 ].
In addition, other groups have considered the effects on MSC populations, such as number, location and differentiation capability[ 1 , 45 ]. There are many in vivo studies which have looked at the amount and quality of bone after LMHFV stimulation. Large and small animal models have been used, as well as clinical human studies. Such studies have covered healthy patients or those with compromised skeletal systems, in particular post-menopausal women.
The efficacy in treating other conditions, such as recovery after stroke[ 50 ], improving the quality of life for disabled children see Matute-Ilorente et al[ 51 ] for a review on this topic or limb function in patients with chronic obstructive pulmonary disease[ 52 ] have also attracted interest. Some studies have also included the ability of LMHFV to improve performance and training in athletes[ 53 ] and cognitive performance in adults with or without attention deficit hyperactivity disorder[ 47 ]. Studies have also used microvibration 20 Hz rocking platform to improve the implantation rates of embryos undergoing IVF treatment[ 54 ].
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In the case of in vivo murine studies, animals are usually confined in a box or cage which can be vibrated in order to apply the LMHFV stimulation[ 1 , 55 - 59 ]. It is worth noting that in such experiments the animals are able to move about freely during the stimulation period. As human participants are usually asked to stand still on a vibrating platform, this may explain some differences in results between the two species.
Compliance in animal trials is assured as their whole environment is often vibrated, but is often low with human patients and may affect the potency of the treatment. The normal movement of the animals during the stimulation, such as running, resting or standing on two legs, will affect the transmissibility of the vibrations through the body, further altering the response to loading.
The breadth of studies reported in the literature cover different vibration conditions, with differing frequencies and accelerations often provided as a multiple of the acceleration due to gravity, g. Ranges include 0. With murine studies, researchers often consider several sites of interest several bones for example due to the ease of analysis after sacrifice.
This was not accompanied by any changes to bone mass, structure or turnover however. In studies of post-menopausal PM women, reported results include small increases in bone mineral density with high compliance 0. The study included 15 min of LMHFV during a 60 min exercise program and also found no significant differences in the BMD of the spine or hip in the subjects.
Such studies suggest that the LMHFV may be having effects on other parts of the musculoskeletal system to improve a variety of measured outcomes. LMHFV has also been shown to cause a small improvement in muscle power in PM women in a short term study, despite low compliance[ 60 ]. Such studies vary in terms of length of treatment, outcomes measured and conditions applied however, creating many difficulties in analysing the usefulness of LMHFV.
These differences are often compounded by low compliance and small study size, making it difficult to draw conclusions about the efficiency of LMHFV on the MSK system. Vibration has been shown to be effective in the prevention of bone loss due to bed rest. Healthy students were subjected to 56 d of bed rest with or without treatment of vibration combined with resistive exercise[ 46 ]. Vibration treatment was found to prevent the changes in muscles size and function, as well as bone volume, compared to the start of the study.
Bone mineral content was also reduced in the control subjects but not those treated. Subjects were also found to have better postural stability compared to controls. Miokovic et al[ 62 ] looked at vibration combined with resistive exercise over 60 d bed rest, finding slightly improved pain scores in the vibrated compared to exercise along groups but no other significant differences.
This work was carried out using an animal model however, other examples of which are discussed later in this review. From the current body of clinical data, LMHFV shows promise in a variety of disease states to improve tissue structure or quality of life. An important factor in the use of whole body vibration as LMHFV is the transmissibility of the vibrations through the rest of the skeleton.
They found that for frequencies lower than 20 Hz, there was low transmission of the forces through the body. However, resonances of the vibrations occurred at higher frequencies, which may help explain why higher frequencies appear to be more effective. They found amplification of the peak amplitude at low frequencies at the ankle, knee, hip and spine. At the spine, this occurred only for 10 Hz acceleration, rising to include 40 Hz by the ankle.
Above 40 Hz, transmissibility was reduced 10 to fold. All subjects reported discomfort for vibration between 20 and 25 Hz for displacements larger than 0. These observations suggest that high acceleration vibrations may not be suitable for LMHFV therapy as patients may be less likely to comply if the treatment was uncomfortable.
The effects of these high acceleration conditions over the longer term are not well studied and it is not known whether this discomfort will translate to negative effects on the MSK system. The trial had a very small number of participants however and the use of external accelerometers may have affected the results. A recent review of the literature concerning osteoporosis treatments[ 67 ] included a section on LMHFV, recommending parameters of 0.
There were also several recommendations regarding contraindications, including cancer, severe diabetes and recent surgery or implantation. The authors suggest that lower frequencies may be unsuitable as they can cause vibration in the internal organs and notes that accelerations higher than 1 g have been observed to cause side effects such as back pain.
There were however no observed changes in diaphyseal bone or muscle parameters. The study noted problems with compliance and stance of the children during the vibration and speculated that variation in posture of the children during vibration therapy may have been one factor in the relatively minor benefits seen. This suggests that transmissibility is an important and unresolved issue for the successful application of LMHFV for therapeutic use. Much as there have been a range of conditions tested in human trials of LMHFV, there are a broad spread of in vivo animal studies.
These cover the use of large animal models in sheep to small animal models in rats and mice. Some studies use healthy animals while others have included ovariectomised animals to emulate post-menopausal conditions. Outcome measures and study lengths also vary greatly and this next section provides an overview of the animal models used so far with LMHFV studies. Bone mineral content and trabecular number were increased, as well as the longitudinal stiffness and strength of the tissue.
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The trabecular spacing was seen to decrease, demonstrating bone adaptation and strengthening. Following on from this work, Judex et al[ 70 ] looked at the same vibration conditions and modelled the trabecular stiffness in different directions from the femoral condoyle.
The models predicted increases in the stiffness in longitudinal, anterior-posterior and medial-lateral directions through the tissue and more uniform distribution of off-axis loading. They also noted that the bone volume and connectedness of the tissue were increased in the vibrated group, demonstrating adaptations requiring bone remodelling. As LMHFV offers a simple, non-invasive treatment with the potential to improve bone mass and structure, there many studies investigating its use for the treatment of osteoporosis.
Therefore there are a large number of animal studies attempting to clarify the possible benefits of vibration by using Ovariectomised OVX or aged rodents. OVX rats or mice are a commonly used animal model of osteoporosis, where the animals develop osteoporosis-like symptoms such as reduced BMD and decrease in trabecular number in the months after ovariectomy[ 71 ]. Significant increases in BMD were found in the femur and tibia vibrated compared to non-vibrated , which gave a non-significant increase in the fracture load of the femur.
The strength of the femur, however, was lower for vibrated animals than for any of the SHAM groups, although there was a non-significant increase for OVX combined with vibration compared to OVX only. Oxlund et al[ 73 ] found that vibration was able to prevent the loss of bending and compressive strength seen in OVX rats.
Vibration 0. A later study also demonstrated the prevention of the detrimental effects of ovariectomy by LMHFV[ 58 ]. Yield load and Young's modulus of the fourth lumbar vertical body were restored to the level of SHAM animals. These changes were accompanied by increases in density particularly for lumbar trabecular bone. Increases were also found in trabecular bone area, trabecular number and width and both the percentage of cortical bone and BMD.
The vibration stimulus was found to be anabolic regardless of the oestrogen levels in the animals.
Effects of immobilization and remobilization on the ankle joint in Wistar rats
LMHFV has also been tested to try and reduce the effects of secondary osteoporosis caused by glucocorticoid treatment[ 74 ]. Three-month-old mice were placed into three groups-control, glucocorticoid treatment and glucocorticoid treatment with LMHFV. Five days per week for 9 wk animals were given saline control group or methylprednisolone glucocorticoid groups injections. Vibrations were applied at 60 Hz during the same period 1 g , 30 min per day, 5 d per week for 9 wk. Glucocorticoids alone reduced weight gain, tibial bone mineral content BMC and trabecular number and increased trabecular spacing compared to controls.
The animals given vibration therapy showed no difference in BMC compared to controls but higher trabecular number and lower spacing than the glucocorticoid only group. This suggests that LMHFV may be a suitable therapy for limiting drug induced changes in bone quality, although further studies on this topic are necessary. A longer term study by Wenger et al[ 59 ] in elderly mice mo-old found no change in the bone volume or strength but increased mineralisation in vibrated animals 0.
Mineralising surface was calculated histologically and the research examined the femur, radius and lumbar vertebrae of the animals. No changes due to vibration were seen in the lumbar spine, however in the femur there was an increase in high density bone. Vibration also reduced the number of pyridinoline crosslinks at both accelerations, suggesting a reduction in the breakdown of collagen.
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High density bone volume was increased at 0. Both vibration conditions showed significant increases in mineralisation surface compared to controls. There was however no significant difference in failure load or stiffness of the radius between any vibration or control condition. This demonstrates that not only are the correct conditions necessary to have an effect on bone turnover, but slight changes to a regimen may be enough to alter the outcome.
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They used 0. They found that the low frequency used 8 Hz increased resorption and reduced mineral apposition, weakening the skeleton. The results also demonstrate that, under the wrong conditions, LMHFV may have negative effects on bone tissue. Judex et al[ 76 ] studied vibration 45 Hz, 0.
They found increased bone formation and mineralisation in the trabecular and periosteal regions of the vibrated tibia. After 4 d in the disuse condition, there were lower levels of mRNA expression for several markers of osteogenesis col-I, osteonectin, osterix and MMP-2 but no changes were seen for the vibrated group.
The work suggests that short periods of vibration may be able to prevent the bone loss and reduction in osteogenesis which occurs during disuse. As has been seen in human studies, the best results in animal models are obtained in subjects with a lower than normal BMD. Animal models often show better results than human studies, which may be due to guaranteed compliance in the animals and lower rates in human cohorts.
There are still many unanswered questions, particularly regarding the efficacy of higher acceleration vibration stimuli. Osteogenesis imperfecta OI , in which the structural protein type 1 collagen is mutated, is another condition which may benefit from LMHFV intervention to improve bone mass and structure. The condition is difficult to treat and while bisphosphonate drugs can be used to inhibit resorption, these affect the normal bone remodelling process and can prevent maintenance of healthy tissue.