The effects of extracorporeal shockwave therapy on osteoporotic changes in a pre-clinical model

Abstract

Introduction Osteoporosis (OP) is a musculoskeletal disease that is defined by reduction in bone porosity, leading to increased risk and prevalence of falls and fractures. Extracorporeal shockwave therapy (ECSWT) has been reported to assist in tissue regeneration and osteogenesis by mechanotransduction. Evidence from prior studies demonstrated that ECSWT facilitated healing in non-unionized and stress fractures, supporting its potential utility as a treatment modality for OP. Bone-specific alkaline phosphatase (BAP) and osteocalcin (OCN) are blood biomarkers that are secreted by bone formation cells. These biomarkers may be effective as a screening tool to measure osteoporotic changes, as dual x-ray absorptiometry is unavailable in remote and rural regions in Canada, or during space travel. Therefore, the purpose of the study was to examine the effects of ECSWT on osteoporotic changes evident on bone microarchitecture computed tomography imaging and blood biomarkers using a pre-clinical model. Methodology The 32 rats in the study were divided into two conditions (ovariectomy and sham surgery) and two treatments (ECSWT and placebo treatment). The treatment groups received five shockwave treatments, once weekly to the right femur (1,000 shockwaves, energy flux density 0.33 mJ/mm2, at 3 Hz). 1 week after the final treatment, blood was extracted, the rats were exsanguinated, and right femur dissected for analysis. The blood biomarkers were analyzed using an enzyme linked immunosorbent assay and femora were examined by computed tomography imaging. A two-way, independent measures analysis of variance was used to analyze changes in blood biomarkers and bone microarchitecture. Results There was a nonsignificant main effect on condition (OVX and sham) and treatment (ECSWT and placebo) on central 10% of bone mineral density (BMD), with a small effect size. There was a statistically significant simple main effect in BMD for 80% of the right femoral diaphysis between treatment groups (ECSWT and placebo; F(1, 28)=7.84, p=.009, η²=.219) with a large effect size. There was a statistically significant main effect in medial cortical bone thickness between condition (OVX and sham surgery; F(1,28)=6.17, p=.019, η²=.180) with a large effect size. There was a statistically significant main effect in lateral cortical bone thickness between condition (OVX and sham surgery; F(1,28)=6.17, p=.019, η²=.180) with a large effect size. There was a nonsignificant main effect on condition (OVX and sham) and treatment (ECSWT and placebo) on anterior cortical bone thickness, with a small effect size. There was a nonsignificant main effect on condition (OVX and sham surgery) and treatment (ECSWT and placebo) on posterior cortical bone thickness, with a small effect size. There was a statistically significant main effect between OVX and sham surgery condition in mediolateral trabecular bone thickness, F(1,28)=12.978, p=.001, η²=.317) with a large effect size. There was a nonsignificant interaction or main effect between OVX and sham surgery condition in anteroposterior trabecular bone thickness, with a small effect size. There was a nonsignificant interaction or main effect between OVX and sham surgery condition in BAP concentration, with a small effect size. There was a statistically significant main effect between OVX and sham surgery condition in OCN concentration (F(1,28)=11.278, p=.002, η2 =.287) with a large effect size. Conclusion ECSWT treatment resulted in nonsignificant changes in cortical bone thickness, trabecular bone thickness, BMD, or biomarker concentrations of OCN and BAP under these experimental conditions. BMD did not decrease as expected from the OVX surgery, and ECSWT did not cause any alteration in bone microarchitecture. However, the measurements used in the present study may not show a comprehensive analysis of trabecular and cortical microarchitecture as the study only assessed trabecular and cortical bone thickness. ECSWT treatment created nonsignificant changes in blood biomarkers. OCN concentration increased in the OVX group when compared to the sham surgery group, suggesting altered bone remodeling following estrogen deficiency. BAP concentration was not significantly altered by OVX. OCN or BAP alone do not reflect OP changes but may be used as an adjunct assessment of altered osteoblast activity. Future studies should consider assessing additional microarchitecture parameters such as bone volume fraction, trabecular number, trabecular separation, and structural model index, using a repeated measures study design comprehensive and comparative analysis of bone microarchitecture.