title: Effects of Roughly Focused Extracorporeal Shock Waves Therapy on the Expressions of Bone Morphogenetic Protein-2 and Osteoprotegerin in Osteoporotic Fracture in Rats.
abstract: BACKGROUND
  Roughly focused extracorporeal shock waves therapy (ESWT) is characterized by a wide focal area, a large therapy zone, easy positioning, and less pain during treatment. The purpose of this study was to investigate the effects of roughly focused ESWT on the expression of osteoprotegerin (OPG) and bone morphogenetic protein-2 (BMP-2) in osteoporotic fractures in rats.
  
  
  METHODS
  Seventy-two female Sprague-Dawley (SD) rats, 3 months old, were divided into sham-operated group (n = 6) and an ovariectomized (OVX) group (n = 66). Sixty OVX SD rats were used as a model of double proximal tibial osteotomy and inner fixation. The osteotomy site in the left tibia was treated with roughly focused ESWT once at an energy density of 0.26 mJ/mm2, 60 doses/min, and 2000 pact quantities. The contralateral right tibia was left untreated and served as a control. Expression of OPG and BMP-2 in the callus of the osteoporotic fracture area was assessed using immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blotting analysis.
  
  
  RESULTS
  Bone mineral density (BMD) at the proximal tibia, femur, and L5 spine was significantly reduced after ovariectomy. BMD of proximal tibia was 12.9% less in the OVX group than that in the sham-operated group. Meanwhile, bilateral oophorectomy resulted in a lower trabecular bone volume fraction (BV/TV) in the proximal tibia of the sham-OVX animals. Three months after bilateral oophorectomy, BV/TV was 14.29% of baseline BV/TV in OVX legs versus 45.91% in the sham-OVX legs (P < 0.001). These data showed that the SD rats became a suitable model of osteoporosis, 3 months after they were OVX. Immunohistochemical analysis showed higher levels of BMP-2 and OPG expression in the treatment group than those in the control group. Compared with the contralateral controls, decreased expression of OPG and BMP-2 at 3 days after roughly focused ESWT, followed by a later increase at 7 days, was indicated by real-time PCR and Western blotting analysis. The OPG messenger RNA (mRNA) expression levels peaked at 6 weeks after the shock wave treatment, paired with a much earlier (at 4 weeks) increase of BMP-2, and declined close to normal at 8 weeks.
  
  
  CONCLUSIONS
  Roughly focused ESWT may promote the expression of OPG and BMP-2 in the osteoporotic fracture area in rats. BMP-2 and OPG may act synergistically and may lead to a significant enhancement of bone formation and remodeling.
authors: Department of Orthopedic Surgery, Nanchang Hongdu Hospital of Traditional Chinese Medicine, Nanchang, Jiangxi 330006, China.
authors: Hai-Ming
authors: HM
authors: Huang
authors: Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.
authors: Xiao-Lin
authors: XL
authors: Li
authors: Department of Orthopedic Surgery, Nanchang Hongdu Hospital of Traditional Chinese Medicine, Nanchang, Jiangxi 330006, China.
authors: Shu-Qiang
authors: SQ
authors: Tu
authors: Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.
authors: Xiao-Feng
authors: XF
authors: Chen
authors: Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.
authors: Chang-Chun
authors: CC
authors: Lu
authors: Department of Orthopedic Surgery, Kunshan First People's Hospital, Suzhou, Jiangsu 215300, China.
authors: Liang-Hua
authors: LH
authors: Jiang
mesh_terms: D000818:Animals; D015519:Bone Density / Q000528:radiation effects; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000378:metabolism / Q000528:radiation effects; D017102:Fracture Healing / Q000528:radiation effects*; D019220:High-Energy Shock Waves; D058866:Osteoporotic Fractures / Q000378:metabolism* / Q000628:therapy*; D053244:Osteoprotegerin / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000378:metabolism / Q000528:radiation effects
chemical_list: D055396:Bone Morphogenetic Protein 2; D053244:Osteoprotegerin