Fibrinolysis as a Target to Enhance Osteoporotic Fracture healing
Refereed conference paper presented and published in conference proceedings


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AbstractBackground & Aim
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, a recent study showed the removal of the hematoma clot was essential for initiation of vascular invasion and fracture healing. The objective of this study is to target fibrinolysis with vibration therapy to enhance healing in a clinically relevant osteoporotic metaphyseal fracture rat model.

Methods
144 six-month-old female Sprague-Dawley rats were randomized to 4 groups: ovariectomized metaphyseal fracture, ovariectomized metaphyseal fracture with low-magnitude high-frequency vibration (LMHFV), sham metaphyseal fracture and sham metaphyseal fracture with LMHFV. LMHFV was 35Hz, peak-to-peak magnitude 0.3g, 20 minutes/day, 5 times/week. Rats were euthanized at 3 days, 1, 2, and 6 weeks. Assessments were Clinical, X-rays, Micro-computed tomography, Histology: Hematoxylin-Eosin (H&E), Safranin O (SO), Martius Scarlet Blue (MSB: stain for fibrin), Immunohistochemistry of callus: tPA, PAI-1, VEGF, ELISA: tPA, PAI-1 (at hamstring muscle and serum) were performed. Mechanical testing was performed at 2 and 6 weeks (n=6/time-point).

Results
All rats achieved healing at 6 weeks. X-ray and Micro-CT showed LMHFV enhanced osteoporotic fracture healing at early stages. Healing was a process of intramembranous ossification with trabecular bone formation. Fibrinolytic profile was improved with immunohistochemistry and ELISA from local muscle and fracture site showing increased tPa, decreased PAI-1 at day 3. Fibrin content from MSB was significantly decreased at day 3 leading to increased angiogenesis at day 7 for vibration groups. LMHFV enhanced biomechanical strength in terms of energy to failure.

Conclusions
Vibration therapy was shown to enhance osteoporotic fracture healing by targeting the fibrinolytic pathway. Enhanced breakdown of the hematoma clot allowed rapid angiogenesis. No complications were observed. This study serves as a platform for future clinical trials.

Acknowledgement
Health and Medical Research Fund (Ref: 04152406)
Acceptance Date06/06/2019
All Author(s) ListWong RMY, Chow SKH, Leung KS, Cheung WH, Cheng JCY
Name of ConferenceAsia Pacific Bone Academy
Start Date of Conference03/08/2019
End Date of Conference04/08/2019
Place of ConferenceTokyo
Country/Region of ConferenceJapan
Year2019
LanguagesEnglish-United States

Last updated on 2019-04-12 at 16:47