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

• Published in: PloS one 2017-02, Vol.12 (2), p.e0171276-e0171276
• Main Authors: Lama, Adriano, Santoro, Anna, Corrado, Bruno, Pirozzi, Claudio, Paciello, Orlando, Pagano, Teresa Bruna, Russo, Sergio, Calignano, Antonio, Mattace Raso, Giuseppina, Meli, Rosaria
• Format: Article
• Language: English
• Subjects: Adiponectin; Adiponectin - genetics; Adiponectin - metabolism; Alkaline phosphatase; Animals; Biocompatibility; Biology and Life Sciences; Biomarkers; Biomedical materials; Bone and Bones - drug effects; Bone and Bones - metabolism; Bone and Bones - pathology; Bone and Bones - radiation effects; Bone Density Conservation Agents - pharmacology; Bone growth; Bone loss; Bone marrow; Bone mineral density; Bone remodeling; Bone resorption; Bone Resorption - etiology; Bone Resorption - genetics; Bone Resorption - metabolism; Bone Resorption - prevention & control; Bone surgery; Cathepsin K; Clinical medicine; Computer architecture; Disease Models, Animal; Dosage and administration; Drug therapy; Estrogen receptors; Female; Femur; Gene expression; Health aspects; High-Energy Shock Waves; Medicine and Health Sciences; Mesenchyme; Metabolism; Neurosciences; Osteoblastogenesis; Osteogenesis; Osteogenesis - drug effects; Osteogenesis - genetics; Osteogenesis - radiation effects; Osteopenia; Osteoporosis; Osteoporosis - drug therapy; Osteoporosis - etiology; Osteoporosis - pathology; Osteoprotegerin; Ovariectomy; Ovariectomy - adverse effects; Parathyroid hormone; Pharmacy; PPAR gamma - metabolism; Public health; Raloxifene; Raloxifene Hydrochloride - pharmacology; Rats; Rodents; Shock waves; Spine; Stem cells; Surgery; Synergistic effect; Transcription, Genetic; Ultrasound; Vertebrae; Veterinary medicine; Weight reduction; Womens health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0171276

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.