Effect of Locally Administered Bisphosphonate on Bone Regeneration and Micro-architecture in a Critical-size Segmental Defect in the Rat Fibula

Bisphosphonates are well-known drugs as inhibitors of bone resorption.  They act on inducing programmed cell death of osteoclasts and this mechanism already has been described in many articles.  Recently, however, many in-vitro studies report that optimal concentration of the bisphosphonate affects not only osteoclasts, but also osteoblasts, that is, it induces the anabolic effects of osteoblast as well.

The purpose of this study was to demonstrate the anabolic effect of bisphosphonates when they were used with Biphasic calcium phosphate(BCP) block(Osspol®; HA 60%, β-TCP 40%, Dongsung, Seoul, South korea), a kind of graft material, topically in a rat fibula defect model.  A more than critical size defect (7mm) of fibula was created in each of 16 male Spraque-Dawley rats.  The control groups are left sides, resected and positioned with saline soaked BCP block(in size 2 x 2 x 8 mm).  On the other hands, the experimental groups are right sides, resected and positioned with Alendronate(ALN, 2.0mg/ml) loaded BCP block. The groups were evaluated using histologic, radiologic, Micro-CT, and statistical methods following 4- and 8-week healing intervals.

Table 3.Diagrams showing the data simply

Among the observed results for both control and experimental groups we can highlight the following:

1. Locally administered bisphosphonates, dissolved from BCP blocks, protect the graft materials from resorption and degradation.

2. Proper concentration of bisphosphonate lead to osteoblastic differentiation inducing bony apposition to the defect sites.

In recent years, many of us have had a focus on the negative effect of bisphosphonate having potential risk of jaw necrosis, but we are concentrating on the other aspect of it in this study.  We could see the positive effects of bisphosphonates for regeneration of bony tissue.  If researchers find out the optimal concentration of bisphosphonate and use it with proper drug delivery systems, it can be one of the best methods to reconstruct various bony defects including oral and maxillofacial area expecting a faster and safer wound healing.

References

Jakobsen, T., Baas, J., Bechtold, J. E., Elmengaard, B., Søballe, K. 2009. "The Effect of Soaking Allograft in Bisphosphonate: A Pilot Dose-response Study". Clinical Orthopaedics and Related Research®468(3): 867-874.

von Knoch, F., Jaquiery, C., Kowalsky, M., Schaeren, S., Alabre, C., Martin, I., Rubash, H. E., Shanbhag, A. S. 2005. "Effects of bisphosphonates on proliferation and osteoblast differentiation of human bone marrow stromal cells". Biomaterials26(34): 6941-6949.