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The Effectiveness of Human Parathyroid Hormone and Low-Intensity Pulsed Ultrasound on the Fracture Healing in Osteoporotic Bones

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Abstract

Osteoporotic fracture has become a major public health problem, and until today, the treatments available are not satisfactory. While there is growing evidence to support the individual treatment of parathyroid hormone (PTH) administration and low-intensity pulsed ultrasound (LIPUS) exposure as respectively systemic and local therapies during osteoporotic fracture healing, their effects have not yet been investigated when introduced concurrently. This study aimed to evaluate the effects of combined treatment with PTH (1–34) and LIPUS on fracture healing in ovariectomized (OVX) rats. Thirty-two, 12-week-old female Sprague–Dawley rats were OVX to induce osteoporosis. After 12 weeks, the rats underwent surgery to create bilateral mid-diaphyseal fractures of proximal tibiae. All animals were randomly divided into 4 groups (n = 8 for each): control group as placebo, PTH group, LIPUS group, and combined group. PTH group had PTH administration at a dose of 30 μg/kg/day for 3 days/week for 6 weeks. LIPUS group received ultrasound 5 days/week for 20 min/day for 6 weeks and combined group had both PTH administration and LIPUS exposure for 6 weeks. Fracture healing was observed weekly by anteroposterior radiography and micro-CT. Five weeks after the fracture, the tibia were harvested to permit histological assessments and at week 6, for mechanical property of the fracture callus. Micro-CT showed that the PTH and combined groups exhibited significantly higher BMD and trabecular bone integrity than control group at weeks 4–6. Radiography, fracture healing score and mean callus area indicated that the combined group revealed better healing processes than the individual groups. Mechanically, bending moment to failure was significantly higher in LIPUS, PTH and combined groups than in control group. These data suggest that the combined treatment of PTH and LIPUS have been shown to accelerate fracture bone healing and enhance bone properties rather than single agent therapy, and may be considered as a treatment remedy for fracture healing in postmenopausal osteoporosis.

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Acknowledgements

This research was supported by Grants-in-Aid 26293436 for Science Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are also grateful to Akira Tabata and Nobuyasu Yamanaka for providing the ultrasound devices and technical support for the experiments and Yukihiro Isogai, PhD for providing PTH [teriparatide, Synthesized human PTH (1-34)].

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Authors and Affiliations

  1. Department of Orthodontics and Dentofacial Orthopedics, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan

    Karima Q. Mansjur, Shingo Kuroda, Takashi Izawa, Yuichi Maeda, Minami Sato, Keiichiro Watanabe, Shinya Horiuchi & Eiji Tanaka

  2. Department of Orthodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia

    Eiji Tanaka

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  1. Karima Q. Mansjur
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Correspondence to Eiji Tanaka.

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Associate Editor Kent Leach oversaw the review of this article.

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Mansjur, K.Q., Kuroda, S., Izawa, T. et al. The Effectiveness of Human Parathyroid Hormone and Low-Intensity Pulsed Ultrasound on the Fracture Healing in Osteoporotic Bones. Ann Biomed Eng 44, 2480–2488 (2016). https://doi.org/10.1007/s10439-015-1533-y

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