Background: Extracorporeal shock wave therapy (ESWT) is widely used in the clinic for non-union of fractures. However, effect of ESWT on longitudinal bone growth has not been well studied. We explored the in vitro and in vivo effects of low/high dose radial shock wave treatment (SWT) on growth plate (GP) cartilage. A positive or negative effect on growth could be harnessed for therapeutic growth modulation while no change establishes safety.
Methods: As a proof of principle, we studied the effects of radial SWT by varying energy levels and frequencies in an ex vivo model of cultured fetal rat metatarsal (n=40) bones. At day fourteen, outcome was assessed by length measurement, histology, and immunohistochemistry. In vivo, immature New Zealand white rabbits (n=3) received a low dose of 1500 impulse/5 Hz/90 mJ, 4 times/month and a high dose of 3000 impulse/5 Hz/180 mJ, 3 times/month on the right distal femur with contralateral limb as untreated control. Changes in GP were evaluated by histomorphometry and immunohistochemistry after 4 weeks. Data are expressed as mean±S.D.
Results: In vitro, high energy group (10 Hz/180 mJ) showed an increase in bone length of 2508±205 μm compared to 1900±555 μm in control bones (P<0.05); increase (P<0.001) in the hypertrophic zone height (504±58 μm) as compared to control (158.8±13.4 μm) was observed. Immunostaining in high energy group revealed upregulation of PCNA, Bcl-x, Bcl-2, Gli1, NFkB and IGF-1 compared to untreated controls (P<0.05). In vivo, high energy group showed increase in cell proliferation (low dose: 79±45 vs 81±4, ns; high dose: 114±9.20 vs 67±0.60, P<0.05); low energy group when compared to control showed increase in thickness of GP cartilage (low dose: 504±90 μm vs 413±65 μm, P<0.05; high dose: 582±123 μm vs 501±26 μm, ns) and area (low dose: 2.20±0.40 μ2 vs 1.80±0.35 μ2, P<0.05; high dose: 2.20±0.61 μ2 vs 1.90±0.25 μ2, P=ns). However final bone length remained unchanged.
Conclusion: High energy radial SWT may stimulate local bone growth by activating Ihh and NFkB pathways in fetal metatarsal bones. In contrast, short-term treatment in rabbits showed a transient increase in GP cartilage area without affecting bone length. Further refining of shock wave doses, location, and duration of treatment are warranted to study any clinically useful impact on longitudinal bone growth.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology