Vibration therapy enhances osteoporotic fracture healing by targeting the fibrinolytic pathway
Refereed conference paper presented and published in conference proceedings

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AbstractIntroduction: It has been long postulated that the fracture hematoma, or fibrin clot, serves as a source of promoting signaling molecules for initiation of healing. However, this long-standing concept has recently been challenged. In fact, a recent study showed fibrin was entirely dispensable and inefficient fibrinolysis caused a derangement in diaphyseal fracture repair in mice. The removal of the hematoma clot was essential for initiation of vascular invasion and fracture healing. Importantly, impaired fibrinolytic activity and bone healing is strongly associated with advanced age and osteoporosis. Therefore, further studies that target fibrinolysis to improve osteoporotic fracture healing are warranted. Tissue plasminogen activator (tPA) is a catalyst that converts plasminogen to plasmin, which degrades the hematoma clot. On the other hand, plasminogen activator inhibitor-1 (PAl-1) inhibits tPA, and both enzymes are expressed in skeletal muscle and endothelial cells. Vibration therapy provides mechanical stimulus to increase physiological responses of muscle activity and perfusion. Clinical studies have proven its effect on increasing tPA and reducing PAl-1 serum concentrations in healthy young men. More importantly, most osteoporotic fractures occur at the metaphyseal region and the effect of vibration therapy on the fibrinolytic pathway in healing is unknown. We hypothesized that vibration therapy enhances fibrinolysis, which accelerates breakdown of the hematoma clot for rapid angiogenesis to improve osteoporotic fracture healing. The primary objective of this study is to target fibrinolysis with vibration therapy to enhance healing in a new clinically relevant osteoporotic metaphyseal fracture model.
Methodology: 144 six-month old female Sprague-Dawley rats (n=144) were obtained from Laboratory Animal Services Center of CUHK. Rats were randomized to 4 groups: ovariectomized metaphyseal fracture (OVX-MF; n=36), ovariectomized metaphyseal fracture with low-magnitude high-frequency vibration (LMHFV) (OVX-MF-VT; n=36), sham metaphyseal fracture (Sham-MF; n=36) and sham metaphyseal fracture with LMHFV (SHAM-MF-VT; n=36). Both OVX-MF and OVX-MF-VT ratsunderwent bilateral ovariectomy (OVX). Sham groups underwent the same procedure but ovaries were left intact. LMHFV was 35Hz vertical vibration, peak-to-peak magnitude 0.3g, 20 minutes/day, 5 times/week. Metaphyseal fracture: after general anesthesia, the left femur was disinfected and draped. A 3 cm skin incision was made over lateral aspect of left thigh and the lateral femur was exposed from lateral condyle to mid-shaft. A 6-hole T-shaped miniplate with two 8mm screws and three 6mm screws were used to fix the plate to distal femur. A small oscillating saw was used to perform an osteotomy at the distal femur. After normal saline irrigation, the wound was closed in layers. Rats were euthanized at 3 days, 1, 2, and 6 weekspost-surgery (n=6 per time-point). Assessments were Clinical, X-rays, Micro-computed tomography, Histology: Hematoxylin-Eosin (H&E), Safranin O (SO: stain for proteoglycans), Martius Scarlet Blue (MSB: stain for fibrin), lmmunohistochemistry: tPA, PAl-1, VEGF (at fracture site), ELISA: tPA, PAl-1 (at hamstring muscle and serum) were performed. Mechanical testing was performed at 2 and 6 weeks (n=6 per time-point). Analysis of variance tests were used to compare means for continuous variables.
All Author(s) ListRMY Wong, VMH Choy, KS Leung, SKH Chow, WH Cheung, JCY Cheng
Name of ConferenceHong Kong Orthopaedic Association 38th Annual Congress 2018 (HKOA 2018)
Start Date of Conference03/11/2018
End Date of Conference04/11/2018
Place of ConferenceHong Kong
Country/Region of ConferenceHong Kong
Proceedings TitleThe Proceeding of Hong Kong Orthopaedic Association 38th Annual Congress 2018 (HKOA 2018)
Place of PublicationHong Kong
Pages32 - 33
LanguagesEnglish-United Kingdom

Last updated on 2019-24-04 at 11:55