In this pilot study, we showed that application of unfocused perioperative shockwave is feasible and without adverse events. However, no effect in terms of bone density increase or bone area could be observed in the forearm based on any of the regions of interest analyzed. Many studies investigated the effects of ESW therapy in animal experiments on bone [
8,
9,
26,
27] and in humans on non-unions [
21,
22,
28‐
30]. Although previous animal experiments reported positive results, in the current study, no effect of shockwave therapy could be demonstrated. It might be that the anabolic effect was already diminished 6 weeks after the UESW treatment. However, since bone turnover and bone resorption processes are rather slow, this is not a likely option. In addition, if the increase is not sustained for more than 6 weeks, it would not be relevant. The most likely reason is that the parameters of the shockwaves used in this trial are not effective. The energy flux density of 0.3 mJ/mm
2 in this clinical study was the highest possible unfocused energy flux with this device and has been shown to be effective with diabetic ulcers [
19]. We speculate that with a higher local dose, there will be an effect on bone content as recently Shi et al. showed an increase of BMD with the use of focused radial shockwave therapy [
31]. As such a focused device only treats a very small area, it is difficult to use this as a therapy to prevent osteoporotic fractures. Unfocused shockwaves, also, might not reach enough depth for the entire bone to be treated [
17]. The study of Shi et al. only included osteoporotic patients and treated them accordingly with bisphosphonates, supplemental vitamin D, and calcium, which may explain the differences as well. Previously, we also demonstrated that the use of bisphosphonates in osteoporotic rats induces stronger effects of shockwave therapy [
10]. Also, Gerdesmeyer et al. demonstrated that pathologic circumstances show different results of shockwave therapy. They demonstrated that patients with low BMC/BMD were more sensitive to shockwave treatment and increased more bone mass compared with subjects that had a normal or high BMC/BMD [
32]. Future research should focus on osteoporotic patients with or without bisphosphonates, and preferably comparing focused and unfocused shockwave therapy. It should also focus on a more potent treatment protocol. One more reason for our negative finding could be that the shockwaves in our study were applied to the distal forearm, where cancellous bone is predominant. Previous bone measurements have shown that shockwave induced bone formation has a more persisted effect on cortical bone [
10,
11]. Also, there is a possibility of a type 2 error, in which case we missed a significant difference due to the low study power in the current study. Although the effect of shockwave therapy was negligible in our study, to draw an definite significant conclusion a study is required with a much larger group of 174 patients per group, as was indicated by the power analysis based on our current findings.
A limitation of the use of shockwave therapy for bone regeneration is the use of anesthesia that is required because of UESW-related pain, in particular with the magnitude of the energy level used in the current study. We applied shockwave therapy during a surgery for another indication where aesthesia was required anyway and concluded that shockwave therapy is safe and non-invasive under the current circumstances.
In conclusion, we have shown that a single treatment with unfocused ESW of 0.3 mJ/mm2 energy flux is not likely to result in increased BMC or BMD of the forearm. However, to draw a final conclusion, a power analysis indicated that a study with 174 patients per group is required to show an effect size of 0.3 with a power of 80%.