Fibrinolysis as a target to enhance osteoporotic fracture healing by vibration therapy in a metaphyseal fracture model

• Published in: Bone & joint research Vol. 10; no. 1; pp. 41 - 50
• Main Authors: Wong, Ronald Man Yeung, Choy, Victoria Man Huen, Li, Jie, Li, Tsz Kiu, Chim, Yu Ning, Li, Meng Chen Michelle, Cheng, Jack Chun Yiu, Leung, Kwok-Sui, Chow, Simon Kwoon-Ho, Cheung, Wing Hoi
• Format: Journal Article
• Language: English
• Published: England British Editorial Society of Bone & Joint Surgery 01.01.2021; The British Editorial Society of Bone & Joint Surgery
• Subjects: Angiogenesis; Animal models; Bone Fracture; Bone healing; Callus; Fibrin; Fibrinolysis; Fractures; Hematoma; lmhfv; Mechanical properties; metaphyseal fracture; Osteoporosis; osteoporotic fracture; Ovariectomy; Plasminogen activator inhibitors; t-Plasminogen activator; vibration therapy; LMHFV; Fibrinolysis; Osteoporotic fracture; Vibration therapy; Metaphyseal fracture
• ISSN: 2046-3758; 2046-3758
• DOI: 10.1302/2046-3758.101.BJR-2020-0185.R1

Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing. A total of 144 rats were randomized to four groups: sham control; sham and LMHFV; ovariectomized (OVX); and ovariectomized and LMHFV (OVX-VT). Fibrinolytic potential was evaluated by quantifying fibrin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) along with healing outcomes at three days, one week, two weeks, and six weeks post-fracture. All rats achieved healing, and x-ray relative radiopacity for OVX-VT was significantly higher compared to OVX at week 2. Martius Scarlet Blue (MSB) staining revealed a significant decrease of fibrin content in the callus in OVX-VT compared with OVX on day 3 (p = 0.020). Mean tPA from muscle was significantly higher for OVX-VT compared to OVX (p = 0.020) on day 3. Mechanical testing revealed the mean energy to failure was significantly higher for OVX-VT at 37.6 N mm (SD 8.4) and 71.9 N mm (SD 30.7) compared with OVX at 5.76 N mm (SD 7.1) (p = 0.010) and 17.7 N mm (SD 11.5) (p = 0.030) at week 2 and week 6, respectively. Metaphyseal fracture healing is enhanced by LMHFV, and one of the important molecular pathways it acts on is fibrinolysis. LMHFV is a promising intervention for osteoporotic metaphyseal fracture healing. The improved mechanical properties, acceleration of fracture healing, and safety justify its role into translation to future clinical studies. Cite this article:  2021;10(1):41-50.