Fracture repair continues to be widely investigated, both within the
clinical realm and at the fundamental research level, in part due to the fact
that 5% to 10% of fractures result in either delayed union or nonunion,
depending on the duration of incomplete healing. Beyond the temporal delay in
repair, nonunions share the same unifying characteristic: all periosteal and
endosteal repair processes have stopped and the fracture will not heal without
surgical intervention. A less-invasive alternative method—low-intensity
pulsed ultrasound—has shown promise as a treatment for delayed unions
and nonunions and as a method to facilitate distraction osteogenesis. In this
paper, we summarize the clinical effectiveness of low-intensity pulsed
ultrasound with regard to fracture repair, treatment of nonunion, and
distraction osteogenesis and we discuss the results of a multitude of
published studies that have sought to elucidate the mechanisms behind that
effectiveness through research on low-intensity pulsed ultrasound exposure on
osteoblasts and osteoblast precursors. When evaluated clinically,
low-intensity pulsed ultrasound was shown to enhance bone repair (most
commonly noted as a decrease in healing time), although variations in patient
population hindered a definitive claim to clinical effectiveness. In vitro
cellular evaluation and in vivo studies on animal models have revealed an
increase in cell proliferation, protein synthesis, collagen synthesis,
membrane permeability, integrin expression, and increased cytosolic
Ca2+ levels as well as other increased indicators of bone repair in
response to low-intensity pulsed ultrasound exposure. Many of the cellular
responses to low-intensity pulsed ultrasound mirror the cellular responses to
fluid-induced shear flow, suggesting a link between the two as one potential
mechanism of action. The considerable amount of information that has been
revealed about the behavior of osteoblasts under low-intensity pulsed
ultrasound exposure suggests that the exact mechanism of action is complex. It
is clear, however, that considerable progress is being made toward uncovering
these mechanisms, which has served to encourage the use of low-intensity
pulsed ultrasound in new applications. It is posited that successful
noninvasive treatment strategies such as low-intensity pulsed ultrasound may
be combined with other conventional and novel tissue-regeneration strategies
to develop new treatments for large-scale bone defects.