Low Intensity Pulsed Ultrasound (LIPUS) for Accelerated Fracture Recovery
Bones have a natural ability to heal after a fracture. The process is complex and involves several stages. In most cases treating fractures involves realigning the bones and taking measures to ensure that they are maintained in the correct position, for instance using a plaster cast or securing them with plates, screws and rods, so that the natural healing process can take place over the following weeks and months.
While recovery from a fracture can take a long time, it is possible to shorten the period considerably. A proven way of achieving this is through the application of low intensity pulsed ultrasound (LIPUS), which has the potential to reduce recovery time significantly.
Here we will first look at the natural cellular processes that take place during bone healing, we will then review some of the latest evidence on how these processes can be accelerated using LIPUS.
Bone structure consists of microscopic channels surrounded by the cortex, a strong layer, and which is surrounded by the periosteum, a tough outer layer. The structure provides strength with low mass, while the channels allow blood to flow through the bone tissue. Bone tissue is continually regenerated (remodelled) to heal damage caused by normal stresses imposed on it, for instance through exercise. The cells involved in this process are bone cells, osteoblasts and osteoclasts. Osteoblasts produce new bone tissue and form bone cells within the bone matrix; while the role of osteoclasts is to re-absorb bone tissue. This remodelling process is the same processes that are called into play during fracture healing.
The fracture healing process involves various stages. These are the reactive phase which includes inflammation and granulation; the reparative phase; and finally the remodelling phase.
Inflammation begins immediately and persists for approximately five days. When the bone fractures the blood vessels bleed into the surrounding tissue forming a hematoma and the bone tissue at the fracture site die releasing cytokines which stimulate the healing process and osteoclasts begin to reabsorb dead bone cells.
No further healing can take place until the bone fragments are realigned, but once they are fibroblasts begin to form granulation tissue between the bone fragments. It is this granulation tissue that provides a foundation for the formation of soft callus.
Next the fibroblast cells in the granulation tissue start to form cartilage and fibrocartilage between the fragments. Initially this soft callus has a weak spongy structure. New blood vessels form and osteoblasts begin to form woven (fibrous) bone, a weak bone structure that connects the fracture fragments. Over the next few weeks the rest of the soft callus is converted to woven bone.
The next stage is the replacement of the woven bone by lamellar bone, which is much stronger. The replacement process involves ossification which involves the laying down of calcium and phosphate to form the hard callus.
After the fracture fragments have been reunited, the next stage is remodelling. This involves a combination of the laying down of bone by the osteoblasts and bone reabsorption by the osteoclasts. The remodelling processes are influenced by the stresses that are placed on the bone.
Although fracture repair usually restores the damaged skeletal organ to its pre-injury cellular composition, structure and biomechanical function, this isn’t always the case; about 10% of fractures will not heal normally (Einhorn & Gerstenfeld , 2015).
The Benefits of LIPUS
Low intensity pulsed ultrasound is a proven way of accelerating the rate of bone fracture recovery (Saltaji, Raza, Kaur, & Flores, 2016) that works under a wide variety of circumstances for many different kinds of bone fracture ranging from stress fractures through to malunions. (Nolte P et al., 2001). In the case of malunions, 86% of the 26 cases studies healed within 22 weeks with the median healing time being 17 weeks, leading the authors to conclude that “Non-invasive ultrasound therapy is useful in the treatment of challenging, established non-unions.”
The evidence is supported by numerous publications which have shown categorically that LIPUS-treated groups showed statistically significantly better healing and that “complications were minimal” (Kwok-Sui Leung et al., 2004). “For delayed union and non-union, the overall success rate of LIPUS therapy is approximately 67% (humerus), 90% (radius/radius-ulna), 82% (femur), and 87% (tibia/tibia-fibula)” (Watanabe, Matsushita, Bhandari , & Zdero , 2010).
What is LIPUS and how does it work?
Low-intensity pulsed ultrasound (LIPUS) is rapidly becoming established as a technique for the acceleration of fracture healing, and it is effective in both new fractures and mal-unions. While ultrasound has been used for clinical purposes for many years, LIPUS is a specific variant of the technology. Typically, the ultrasound frequency is 1.5 MHz; the pulse width is 200 microseconds and is repeated at a frequency of 1 kHz with an intensity of 30 mW/cm2.
As yet, the precise mechanism through which LIPUS accelerates bone healing is still the subject of much research, though our understanding of the processes is continually improving. One mechanism that has been identified involves the promotion of cartilage healing by inducing chondrogenic progenitor cell (CPC) migration to injured sites. This is likely to prevent or delay the onset of post-traumatic osteoarthritis (Jang Kee et.al., 2014).
Other research (Lei H et.al., 2014) has shown that the mechanisms “may be associated with the upregulation of cell proliferation through activation of integrin receptors and Rho/ROCK/Src/ERK signalling pathway, and with promoting multi-lineage differentiation of mesenchyme stem/progenitor cell lines through ROCK-Cot/Tpl2-MEK-ERK signalling pathway”. However, the authors also point out that much more effort is needed to identify the cellular and molecular mechanisms and biomedical applications of LIPUS on human body.
More recently (Suzuki N. et.al., 2016) it has been demonstrated that LIPUS causes apoptosis (cell death) in osteoclasts and that LIPUS attenuates the release of collagen and reduces apoptosis of chondrocytes in the cartilage matrix as well as modifying the synovial fluid (Jia L. et. al., 2016).
NICE has published guidance on the use of LIPUS for the promotion of fracture healing (NICE, 2010) and states that “Current evidence on the efficacy of low-intensity pulsed ultrasound to promote fracture healing is adequate to show that this procedure can reduce fracture healing time and gives clinical benefit, particularly in circumstances of delayed healing and fracture non-union. There are no major safety concerns.”
Although the mechanisms through which it works are still not fully understood, there is now no doubt that LIPUS really does accelerate the healing of bone fracture, and by a considerable degree. It is also highly beneficial for non-union fractures.
Given that the treatment is both effective and safe, there is every reason to embrace it as a way to rapid recovery, especially in circumstances where shorter healing times are vital.
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Einhorn , T., & Gerstenfeld , L. (2015). Fracture healing: mechanisms and interventions. Nature Reviews Rheumatology , 45–54.
Jang Kee et.al. (2014). Low-Intensity Pulsed Ultrasound Promotes Chondrogenic Progenitor Cell Migration via Focal Adhesion Kinase Pathway. Ultrasound in Medicine & Biology, 1177–1186.
Jia L. et. al. (2016). Matrix Degradation via Decreasing Chondrocyte Apoptosis and Inflammatory Mediators in a Surgically Induced Osteoarthritic Rabbit Model. Ultrasound in Medicine & Biology, 208–219.
Kwok-Sui Leung et al. (2004). Complex tibial fracture outcomes following treatment with low-intensity pulsed ultrasound. Ultrasound in Medicine & Biology, 30(3), 389–395.
Lei H et.al. (2014). The characteristics and therapeutic applications of low-intensity pulsed ultrasound. Translational Andrology and Urology .
NICE. (2010, December). Low-intensity pulsed ultrasound to promote fracture healing. Retrieved from NICE Guidance: https://www.nice.org.uk/guidance/ipg374/chapter/1-Guidance
Nolte P et al. (2001). Low-Intensity Pulsed Ultrasound in the Treatment of Nonunions. Journal of Trauma-Injury Infection & Critical Care, 693-703.
Oryan, A., Monazzah, S., & Bigham-Sadegh, A. (2015). Bone Injury and Fracture Healing Biology. Biomedical and Environmental Sciences, 28(1), 57–71.
Saltaji, H., Raza, H., Kaur, H., & Flores, C. (2016). Effect of Low-Intensity Pulsed Ultrasound on Distraction Osteogenesis Treatment Time. American Institute of Ultrasound in Medicine, 349-358 .
Suzuki N. et.al. (2016). Low-intensity pulsed ultrasound induces apoptosis in osteoclasts. Comparative Biochemistry and Physiology , 26-31.
Watanabe, Y., Matsushita, T., Bhandari , M., & Zdero , R. (2010). Ultrasound for fracture healing: current evidence. J Orthop Trauma, 56-61.