CORR Insights®: Radial Extracorporeal Shock Wave Treatment Promotes Bone Growth and Chondrogenesis in Cultured Fetal Rat Metatarsal Bones

Where Are We Now?

The most common use of extracorporeal shock wave treatment (ESWT) is for lithotripsy, for which efficacy and safety is well-established. Orthopaedic surgeons have reported the use of ESWT in several contexts, particularly the treatment of plantar fasciitis and the healing of fractures, but our knowledge on its use in children is rather sparse [2, 3]. For example, researchers have used animal models to study the effect of ESWT upon the growth plate [1], but the long-term effect of ESWT, either radial or focal, upon the active physis remains, for the most part, unknown.

Because growth disturbances can take many years to develop and can be difficult to treat, we need to know more about the effects of ESWT upon growing bones if we are to utilize this modality for treatment in children. It is appropriate, therefore, to go back to the laboratory to get as much information as we can.

Ramesh and colleagues [4] have done just that, using a model that isolates the effects of radial ESWT (rESWT) from systemic influences, therefore allowing study of rESWT results that are intrinsic to the local tissues. They demonstrated that, even in the absence of systemic growth factors, growth-promoters within the rat metatarsal are upregulated, and these factors are associated with a measurable increase in physeal growth. These results are consistent with the possibility that rESWT may be useful in promoting increased growth, but they by no means prove either the safety or the efficacy of this technique.

Like all high-quality research, their study yields more questions than it answers.

Where Do We Need To Go?

There is quite a difference between a fetal rat’s metatarsal and a child’s knee. Size is the most obvious difference, and when one is speaking of energy imparted from outside the body by shock waves, size matters. The physics of radial waves passing through non-homogeneous tissues should logically ensure inhomogeneity in the delivery of energy to these tissues. In the fetal rat metatarsal, spatial differences in the delivery of energy are probably irrelevant. In a child’s femur, these differences might lead to focal differences in growth, either creating areas within the physis that overgrow or areas that undergrow in response to rESWT.

Species differences are also important. The rat physis has a particularly well-defined zone architecture. The human physis is less well-defined, with the zone of peripheral calcification and the zone of hypertrophy, for example, being less clearly differentiated. The distribution of energy release from rESWT is likely different in humans.

The mechanism of rESWT induction of growth needs to be further studied. The rESWT, after all, delivers a measured trauma to the tissues. We need to know what mechanical effects result from such trauma. Does it cause microfractures of the matrix? Is there intracellular damage to organelles? Is the cellular surface disrupted from dendrites torn loose where they enter the canaliculi?

Ramesh and colleagues [4] have evaluated what occurs in the absence of systemic influences and vascularity. While this technique is useful scientifically, the clinical situation is different. We need to know what differences in outcome might be expected in physes modulated by systemic hormones and circulating growth factors. In addition, while the current study evaluates the earliest results of rESWT, we still do not know whether the increased physeal width and metatarsal growth detected would persist or reverse with time.

Finally, most (but not all) growth problems in children result from abnormal growth plates, not normal ones. The efficacy of rESWT to abnormal growth plates is an entirely different story that may be difficult to sort out.

How Do We Get There?

The following routes might clarify some of these issues. First, researchers should search for anatomic changes in the physis and surrounding matrix immediately following rESWT with both standard and electron microscopy in the fetal rat metatarsal model. Repeat this process using a larger animal model such as a rabbit, with an increased amplitude appropriate to the size of the physis.

Next, I recommend taking samples for electron and standard microscopy in a larger animal model from the surface, mid-physis, and in-between in order to search for regional differences in anatomic effects of the rESWT. Researchers could then correlate these effects with measurements of the amplitude of shock in the same areas.

With appropriate informed consent, researchers could then study the results of rESWT on live human physes taken during removal of polydactylic digits.

If the above steps work, investigators could use animal models in which angulation is induced by focal ESWT to a portion of a normal growth plate. Can the angulation so induced then be reserved by focal ESWT to the growth plate on the concave side?

Only if the above animal models succeed should therapy be considered in a human child.