Extracorporeal shock waves alone or combined with raloxifene promote bone formation and suppress resorption in ovariectomized rats

PLoS One. 2017 Feb 3;12(2):e0171276. doi: 10.1371/journal.pone.0171276. eCollection 2017.

Abstract

Osteoporosis is a metabolic skeletal disease characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. We examined the beneficial effect of shock waves (SW) alone or in combination with raloxifene (RAL) on bone loss in ovariectomized rats (OVX). Sixteen weeks after surgery, OVX were treated for five weeks with SW at the antero-lateral side of the right hind leg, one session weekly, at 3 Hz (EFD of 0.33 mJ/mm2), or with RAL (5 mg/kg/die, per os) or with SW+RAL. Sera, femurs, tibiae and vertebrae were sampled for following biochemical and histological analysis. SW, alone or combined with RAL, prevented femur weight reduction and the deterioration of trabecular microarchitecture both in femur and vertebrae. All treatments increased Speed of Sound (SoS) values, improving bone mineral density, altered by OVX. Serum parameters involved in bone remodeling (alkaline phosphatase, receptor activator of nuclear factor kappa-B ligand, osteoprotegerin) and osteoblast proliferation (PTH), altered by ovariectomy, were restored by SW and RAL alone or in combination. In tibiae, SW+RAL significantly reduced cathepsin k and TNF-α levels, indicating the inhibition of osteoclast activity, while all treatments significantly increased runt-related transcription factor 2 and bone morphogenetic-2 expression, suggesting an increase in osteoblastogenic activity. Finally, in bone marrow from tibiae, SW or RAL reduced PPARγ and adiponectin transcription, indicating a shift of mesenchymal cells toward osteoblastogenesis, without showing a synergistic effect. Our data indicate SW therapy, alone and in combination with raloxifene, as an innovative strategy to limit the hypoestrogenic bone loss, restoring the balance between bone formation and resorption.

MeSH terms

  • Adiponectin / genetics
  • Adiponectin / metabolism
  • Animals
  • Biomarkers
  • Bone Density Conservation Agents / pharmacology*
  • Bone Resorption / etiology
  • Bone Resorption / genetics
  • Bone Resorption / metabolism
  • Bone Resorption / prevention & control*
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Bone and Bones / radiation effects
  • Disease Models, Animal
  • Female
  • High-Energy Shock Waves*
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Osteogenesis / radiation effects*
  • Osteoporosis / drug therapy
  • Osteoporosis / etiology
  • Osteoporosis / pathology
  • Ovariectomy / adverse effects
  • PPAR gamma / metabolism
  • Raloxifene Hydrochloride / pharmacology*
  • Rats
  • Transcription, Genetic

Substances

  • Adiponectin
  • Biomarkers
  • Bone Density Conservation Agents
  • PPAR gamma
  • Raloxifene Hydrochloride

Grant support

This study was supported by Storz Medical AG, Tagerwilen, Switzerland. This external company provided an economical support for fulfillment of the study, contributing to purchase of laboratory equipment. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript which did not contribute to experimental model design, experiment realization, data analysis, results interpretation and manuscript writing. There was no additional external funding received for this study.