Osteoporos Sarcopenia.  2017 Dec;3(4):185-191. 10.1016/j.afos.2017.11.001.

Effects of combined therapy of alendronate and low-intensity pulsed ultrasound on metaphyseal bone repair after osteotomy in the proximal tibia of glucocorticoid-induced osteopenia rats

• Kawano T
• Miyakoshi
• Kasukawa Y
• Hongo M
• Tsuchie H
• Sato C
• Fujii M
• Suzuki M
• Akagawa M
• Ono Y
• Yuasa Y
• Nagahata I
• Shimada Y

• KMID: 2404902
• DOI: http://doi.org/10.1016/j.afos.2017.11.001

Abstract

OBJECTIVES
Glucocorticoid (GC) treatment inhibits activation of runt-related transcription factor 2 (Runx2), which is essential for osteoblast differentiation from stem cells. As a result, GC treatment results in bone loss, GC-induced osteoporosis (GIO), elevated fracture risk, and delayed bone healing. Bisphosphonates such as alendronate (ALN) are recommended for treating or preventing GIO, and lowintensity pulsed ultrasound (LIPUS) facilitates fracture healing and maturation of regenerated bone. Combined therapy with ALN and LIPUS may stimulate cancellous bone healing in GIO rats. Here, we examined the effect of ALN and LIPUS on cancellous bone osteotomy repair in the proximal tibia of GIO rats.
METHODS
Prednisolone (10 mg/kg body weight/day) was administered for 4 weeks to induce GIO in 6-month-old female Sprague-Dawley rats. Tibial osteotomy was then performed and daily subcutaneous injection of ALN (1-µg/kg body weight) was subsequently administered alone or in combination with LIPUS (20 min/day) for 2 or 4 weeks.
RESULTS
ALN significantly increased bone mineral density (BMD) at 2 and 4 weeks, and ALN + LIPUS significantly increased BMD at 4 weeks. Bone union rates were significantly increased after 2 and 4 weeks ALN and ALN + LIPUS treatment. Lastly, ALN and ALN + LIPUS significantly increased the proportion of Runx2 positive cells at 4 weeks.
CONCLUSIONS
ALN monotherapy and combined ALN and LUPUS treatment augmented BMD and stimulated cancellous bone repair with increased Runx2 expression at the osteotomy site in GIO rats. However, the combined treatment had no additional effect on cancellous bone healing compared to ALN monotherapy.

Keyword

Glucocorticoid; Osteoporosis; Bisphosphonate

MeSH Terms

Alendronate*
Animals
Bone Density
Bone Diseases, Metabolic*
Diphosphonates
Female
Fracture Healing
Humans
Infant
Injections, Subcutaneous
Osteoblasts
Osteoporosis
Osteotomy*
Prednisolone
Rats*
Rats, Sprague-Dawley
Stem Cells
Tibia*
Transcription Factors
Ultrasonic Waves*
Alendronate
Diphosphonates
Prednisolone
Transcription Factors